Patent Description:
Certain embodiments disclosed herein relate to adaptors for coupling with medicinal vials, and components thereof.

It is a common practice to store medicines or other medically related fluids in vials or other containers. In some instances, the medicines or fluids so stored are therapeutic if injected into the bloodstream, but harmful if inhaled or if contacted by exposed skin. Certain known systems for extracting potentially harmful medicines from vials suffer from various drawbacks. Document <CIT> discloses a pressure-regulating vial adaptor including the technical features of the preamble of claim <NUM>.

The invention is defined by the independent claim.

Various embodiments are depicted in the accompanying drawings for illustrative purposes, and should in no way be interpreted as limiting the scope of the embodiments. In addition, various features of different disclosed embodiments can be combined to form additional embodiments, which are part of this disclosure.

The scope of the claims appended hereto is not limited by any of the particulars embodiments below.

The drawing showing certain embodiments can be semi-diagrammatic and not to scale and, particularly, some of the dimensions are for the clarity of presentation and are shown greatly exaggerated in the drawings.

For expository purposes, 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 device being described is used or the method being described is performed, regardless of its orientation. The term "floor" floor can be interchanged with the term "ground. " The term "vertical" refers to a direction perpendicular to the horizontal as just defined. Terms such as "above," "below," "bottom," "top," "side," "higher," "lower," "upper," "over," and "under," are defined with respect to the horizontal plane.

Numerous medicines and other therapeutic fluids are stored and distributed in medicinal vials or other containers of various shapes and sizes. These vials are hermetically sealed to prevent contamination or leaking of the stored fluid. The pressure differences between the interior of the sealed vials and the particular atmospheric pressure in which the fluid is later removed often give rise to various problems, as well as the release of potentially harmful vapors.

For instance, introducing a piercing member of a vial adaptor through the septum of a vial can cause the pressure within the vial to rise. This pressure increase can cause fluid to leak from the vial at the interface of the septum and piercing member or at the attachment interface of the adaptor and a medical device, such as a syringe. Also, it can be difficult to withdraw an accurate amount of fluid from a sealed vial using an empty syringe, or other medical instrument, because the fluid may be naturally urged back into the vial once the syringe plunger is released. Furthermore, as the syringe is decoupled from the vial, pressure differences can often cause an amount of fluid to spurt from the syringe or the vial.

Moreover, in some instances, introducing a fluid into the vial can cause the pressure to rise in the vial. For example, in certain cases it can be desirable to introduce a solvent (such as sterile saline) into the vial, e.g., to reconstitute a lyophilized pharmaceutical in the vial. Such introduction of fluid into the vial can cause the pressure in the vial to rise above the pressure of the surrounding environment, which can result in fluid leaking from the vial at the interface of the septum and piercing member or at the attachment interface of the adaptor and a medical device, such as a syringe. Further, the increased pressure in the vial can make it difficult to introduce an accurate amount of the fluid into the vial with a syringe, or other medical instrument. Also, should the syringe be decoupled from the vial when the pressure inside the vial is greater than the surrounding pressure (e.g., atmospheric), the pressure gradient can cause a portion of the fluid to spurt from the vial.

Additionally, in many instances, air bubbles are drawn into the syringe as fluid is withdrawn from the vial. Such bubbles are generally undesirable as they could result in an embolus if injected into a patient. To rid a syringe of bubbles after removal from the vial, medical professionals often flick the syringe, gathering all bubbles near the opening of the syringe, and then forcing the bubbles out. In so doing, a small amount of liquid is usually expelled from the syringe as well. Medical personnel generally do not take the extra step to re-couple the syringe with the vial before expelling the bubbles and fluid. In some instances, this may even be prohibited by laws and regulations. Such laws and regulations may also necessitate expelling overdrawn fluid at some location outside of the vial in certain cases. Moreover, even if extra air or fluid were attempted to be reinserted in the vial, pressure differences can sometimes lead to inaccurate measurements of withdrawn fluid.

To address these problems caused by pressure differentials, medical professionals frequently pre-fill an empty syringe with a precise volume of ambient air corresponding to the volume of fluid that they intend to withdraw from the vial. The medical professionals then pierce the vial and expel this ambient air into the vial, temporarily increasing the pressure within the vial. When the desired volume of fluid is later withdrawn, the pressure differential between the interior of the syringe and the interior of the vial is generally near equilibrium. Small adjustments of the fluid volume within the syringe can then be made to remove air bubbles without resulting in a demonstrable pressure differential between the vial and the syringe. However, a significant disadvantage to this approach is that ambient air, especially in a hospital setting, may contain various airborne viruses, bacteria, dust, spores, molds, and other unsanitary and harmful contaminants. The pre-filled ambient air in the syringe may contain one or more of these harmful substances, which may then mix with the medicine or other therapeutic fluid in the vial. If this contaminated fluid is injected directly into a patient's bloodstream, it can be particularly dangerous because it circumvents many of the body's natural defenses to airborne pathogens. Moreover, patients who need the medicine and other therapeutic fluids are more likely to be suffering from a diminished infection-fighting capacity.

In the context of oncology and certain other drugs, all of the foregoing problems can be especially serious. Such drugs, although helpful when injected into the bloodstream of a patient, can be extremely harmful if inhaled or touched. Accordingly, such drugs can be dangerous if allowed to spurt unpredictably from a vial due to pressure differences. Furthermore, these drugs are often volatile and may instantly aerosolize when exposed to ambient air. Accordingly, expelling a small amount of such drugs in order to clear a syringe of bubbles or excess fluid, even in a controlled manner, is generally not a viable option, especially for medical personnel who may repeat such activities numerous times each day.

Some devices use rigid enclosures for enclosing all or a portion of a volume-changing component or region for assisting in regulating pressure within a container. Although such enclosures can provide rigidity, they generally make the devices bulky and unbalanced. Coupling such a device with a vial generally can create a top-heavy, unstable system that is prone to tipping-over and possibly spilling the contents of the device and/or the vial.

Indeed, certain of such coupling devices include relatively large and/or heavy, rigid components that are cantilevered or otherwise disposed a distance from of the axial center of the device, thereby exacerbating the tendency for the device to tip-over.

Additionally, such rigid enclosures can increase the size of the device, which can require an increase in material to form the device and otherwise increase costs associated manufacturing, transporting, and/or storing the device. Further, such rigid enclosures can hamper the ability of the device to expand or contract to deliver a regulating fluid to the vial. No feature, structure, or step disclosed herein is essential or indispensible.

<FIG> is a schematic illustration of a container <NUM>, such as a medicinal vial, that can be coupled with an accessor <NUM> and a regulator <NUM>. In certain arrangements, the regulator <NUM> allows the removal of some or all of the contents of the container <NUM> via the accessor <NUM> without a significant change of pressure within the container <NUM>.

In general, the container <NUM> is hermetically sealed to preserve the contents of the container <NUM> in a sterile environment. The container <NUM> can be evacuated or pressurized upon sealing. In some instances, the container <NUM> is partially or completely filled with a liquid, such as a drug or other medical fluid. In such instances, one or more gases can also be sealed in the container <NUM>. In some instances, a solid or powdered substance, such as a lyophilized pharmaceutical, is disposed in the container <NUM>.

The accessor <NUM> generally provides access to contents of the container <NUM> such that the contents may be removed or added to. In certain arrangements, the accessor <NUM> includes an opening between the interior and exterior of the container <NUM>. The accessor <NUM> can further comprise a passageway between the interior and exterior of the container <NUM>. In some configurations, the passageway of the accessor <NUM> can be selectively opened and closed. In some arrangements, the accessor <NUM> comprises a conduit extending through a surface of the container <NUM>. The accessor <NUM> can be integrally formed with the container <NUM> prior to the sealing thereof or introduced to the container <NUM> after the container <NUM> has been sealed.

In some configurations, the accessor <NUM> is in fluid communication with the container <NUM>, as indicated by an arrow <NUM>. In certain of these configurations, when the pressure inside the container <NUM> varies from that of the surrounding environment, the introduction of the accessor <NUM> to the container <NUM> causes a transfer through the accessor <NUM>. For example, in some arrangements, the pressure of the environment that surrounds the container <NUM> exceeds the pressure within the container <NUM>, which may cause ambient air from the environment to ingress through the accessor <NUM> upon insertion of the accessor <NUM> into the container <NUM>. In other arrangements, the pressure inside the container <NUM> exceeds that of the surrounding environment, causing the contents of the container <NUM> to egress through the accessor <NUM>.

In some configurations, the accessor <NUM> is coupled with an exchange device <NUM>. In certain instances, the accessor <NUM> and the exchange device <NUM> are separable. In some instances, the accessor <NUM> and the exchange device <NUM> are integrally formed. The exchange device <NUM> is configured to accept fluids and/or gases from the container <NUM> via the accessor <NUM>, to introduce fluids and/or gases to the container <NUM> via the accessor <NUM>, or to do some combination of the two. In some arrangements, the exchange device <NUM> is in fluid communication with the accessor <NUM>, as indicated by an arrow <NUM>. In certain configurations, the exchange device <NUM> comprises a medical instrument, such as a syringe.

In some instances, the exchange device <NUM> is configured to remove some or all of the contents of the container <NUM> via the accessor <NUM>. In certain arrangements, the exchange device <NUM> can remove the contents independent of pressure differences, or lack thereof, between the interior of the container <NUM> and the surrounding environment. For example, in instances where the pressure outside of the container <NUM> exceeds that within the container <NUM>, an exchange device <NUM> comprising a syringe can remove the contents of the container <NUM> if sufficient force is exerted to extract the plunger from the syringe. The exchange device <NUM> can similarly introduce fluids and/or gases to the container <NUM> independent of pressure differences between the interior of the container <NUM> and the surrounding environment.

In certain configurations, the regulator <NUM> is coupled with the container <NUM>. The regulator <NUM> generally regulates the pressure within the container <NUM>. As used herein, the term "regulate," or any derivative thereof, is a broad term used in its ordinary sense and includes, unless otherwise noted, any active, affirmative, or positive activity, or any passive, reactive, respondent, accommodating, or compensating activity that tends to effect a change. In some instances, the regulator <NUM> substantially maintains a pressure difference, or equilibrium, between the interior of the container <NUM> and the surrounding environment. As used herein, the term "maintain," or any derivative thereof, is a broad term used in its ordinary sense and includes the tendency to preserve an original condition for some period, with some small degree of variation permitted as may be appropriate in the circumstances. In some instances, the regulator <NUM> maintains a substantially constant pressure within the container <NUM>. In certain instances, the pressure within the container <NUM> varies by no more than about <NUM>,<NUM> kpa (<NUM> psi = <NUM>,89kpa will be used in this patent specification), no more than about <NUM> psi, no more than about <NUM> psi, no more than about <NUM> psi, or no more than about <NUM> psi. In still further instances, the regulator <NUM> equalizes pressures exerted on the contents of the container <NUM>. As used herein, the term "equalize," or any derivative thereof, is a broad term used in its ordinary sense and includes the tendency for causing quantities to be the same or close to the same, with some small degree of variation permitted as may be appropriate in the circumstances. In certain configurations, the regulator <NUM> is coupled with the container <NUM> to allow or encourage equalization of a pressure difference between the interior of the container <NUM> and some other environment, such as the environment surrounding the container <NUM> or an environment within the exchange device <NUM>. In some arrangements, a single device comprises the regulator <NUM> and the accessor <NUM>. In other arrangements, the regulator <NUM> and the accessor <NUM> are separate units.

The regulator <NUM> is generally in communication with the container <NUM>, as indicated by an arrow <NUM>, and a reservoir <NUM>, as indicated by another arrow <NUM>. In some configurations, the reservoir <NUM> comprises at least a portion of the environment surrounding the container <NUM>. In certain configurations, the reservoir <NUM> comprises a container, canister, bag, or other holder dedicated to the regulator <NUM>. As used herein, the term "bag," or any derivative thereof, is a broad term used in its ordinary sense and includes, for example, any sack, balloon, bladder, receptacle, enclosure, diaphragm, or membrane capable of expanding and/or contracting, including structures comprising a flexible, supple, pliable, resilient, elastic, and/or expandable material. In some embodiments, the reservoir <NUM> includes a gas and/or a liquid. As used herein, the term "flexible," or any derivative thereof, is a broad term used in its ordinary sense and describes, for example, the ability of a component to bend, expand, contract, fold, unfold, or otherwise substantially deform or change shape when fluid is flowing into or out of the container <NUM> (e.g., via the accessor <NUM>). Also, as used herein, the term "rigid," or any derivative thereof, is a broad term used in its ordinary sense and describes, for example, the ability of a component to generally avoid substantial deformation under normal usage when fluid is flowing into or out of the container <NUM> (e.g., via the accessor <NUM>).

In certain embodiments, the regulator <NUM> provides fluid communication between the container <NUM> and the reservoir <NUM>. In certain of such embodiments, the fluid in the reservoir <NUM> includes mainly gas so as not to appreciably dilute liquid contents of the container <NUM>. In some arrangements, the regulator <NUM> comprises a filter to purify or remove contaminants from the gas or liquid entering the container <NUM>, thereby reducing the risk of contaminating the contents of the container <NUM>. In certain arrangements, the filter is hydrophobic such that air can enter the container <NUM> but fluid cannot escape therefrom. In some configurations, the regulator <NUM> comprises an orientation-actuated or orientation-sensitive check valve which selectively inhibits fluid communication between the container <NUM> and the filter. In some configurations, the regulator <NUM> comprises a check valve which selectively inhibits fluid communication between the container <NUM> and the filter when the valve and/or the container <NUM> are oriented so that the regulator <NUM> is held above (e.g., further from the floor than) the regulator <NUM>.

In some embodiments, the regulator <NUM> prevents fluid communication between the container <NUM> and the reservoir <NUM>. In certain of such embodiments, the regulator <NUM> serves as an interface between the container <NUM> and the reservoir <NUM>. In some arrangements, the regulator <NUM> comprises a substantially impervious bag for accommodating ingress of gas and/or liquid to the container <NUM> or egress of gas and/or liquid from the container <NUM>.

As schematically illustrated in <FIG>, in certain embodiments, the accessor <NUM>, or some portion thereof, is located within the container <NUM>. As detailed above, the accessor <NUM> can be integrally formed with the container <NUM> or separate therefrom. In some embodiments, the regulator <NUM>, or some portion thereof, is located outside the container <NUM>. In some arrangements, the regulator <NUM> is integrally formed with the container <NUM>. It is possible to have any combination of the accessor <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM> and/or the regulator <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM>.

In certain embodiments, the accessor <NUM> is in fluid communication with the container <NUM>. In further embodiments, the accessor <NUM> is in fluid communication with the exchange device <NUM>, as indicated by the arrow <NUM>.

The regulator <NUM> can be in fluid or non-fluid communication with the container <NUM>. In some embodiments, the regulator <NUM> is located entirely outside the container <NUM>. In certain of such embodiments, the regulator <NUM> comprises a closed bag configured to expand or contract external to the container <NUM> to maintain a substantially constant pressure within the container <NUM>. In some embodiments, the regulator <NUM> is in communication, either fluid or non-fluid, with the reservoir <NUM>, as indicated by the arrow <NUM>.

As schematically illustrated in <FIG>, in certain embodiments, the accessor <NUM>, or some portion thereof, can be located within the container <NUM>. In some embodiments, the accessor <NUM>, or some portion thereof, can be located outside the container <NUM>. In some embodiments, a valve <NUM>, or some portion thereof, can be located outside the container <NUM>. In some embodiments, the valve <NUM>, or some portion thereof, can be located within the container <NUM>. In some embodiments, the regulator <NUM> is located entirely outside the container <NUM>. In some embodiments, the regulator <NUM>, or some portion thereof, can be located within the container <NUM>. It is possible to have any combination of the accessor <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM> and/or the valve <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM>. It is also possible to have any combination of the accessor <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM> and/or the regulator <NUM>, or some portion thereof, entirely within, partially within, or outside of the container <NUM>.

The accessor <NUM> can be in fluid communication with the container <NUM>, as indicated by the arrow <NUM>. In some embodiments, the accessor <NUM> can be in fluid communication with the exchange device <NUM>, as indicated by the arrow <NUM>.

In certain embodiments, the regulator <NUM> can be in fluid or non-fluid communication with a valve <NUM>, as indicated by the arrow <NUM>. In some embodiments, the valve <NUM> can be integrally formed with the container <NUM> or separate therefrom. In some embodiments, the valve <NUM> can be integrally formed with the regulator <NUM> or separate therefrom. In certain embodiments, the valve <NUM> can be in fluid or non-fluid communication with the container <NUM>, as indicated by the arrow <NUM>.

In some embodiments the regulator <NUM> can be in fluid or non-fluid communication with the ambient surroundings, as indicated by the arrow 35A. In some embodiments, the regulator <NUM> can be in fluid or non-fluid communication with a reservoir <NUM>, as indicated by the arrow 35B. In some embodiments, the reservoir <NUM> can comprise a bag or other flexible enclosure. In some embodiments, the reservoir <NUM> comprises a rigid container surrounding a flexible enclosure. In some embodiments, the reservoir <NUM> comprises a partially-rigid enclosure.

According to some configurations, the regulator <NUM> can comprise a filter. In some embodiments, the filter can selectively inhibit passage of liquids and/or contaminants between the valve <NUM> and the reservoir <NUM> or the ambient surroundings. In some embodiments, the filter can selectively inhibit passage of liquids and/or contaminants between the reservoir <NUM> or ambient surroundings and the valve <NUM>.

In some embodiments, the valve <NUM> can be a one-way check valve. In some embodiments, the valve <NUM> can be a two-way valve. According to some configurations, the valve <NUM> can selectively inhibit liquid communication between the filter and/or reservoir <NUM> and the container <NUM>. In some embodiments, the valve <NUM> can selectively inhibit liquid communication between the container <NUM> and the filter and/or reservoir <NUM> when the container <NUM> is oriented above the exchange device <NUM>.

As schematically illustrated in <FIG> and <FIG>, in certain embodiments, the reservoir <NUM> can be located at least partially within the regulator <NUM>. The regulator <NUM> can be in fluid communication with the container <NUM>, as illustrated by arrows <NUM> and <NUM>. In some embodiments, a valve <NUM> is located in the fluid path between the container <NUM> and the regulator <NUM>. The regulator <NUM> can be configured to maintain a substantially constant pressure within the container <NUM> as fluid is introduced into and/or withdrawn from the vial <NUM>. For example, in some embodiments, the reservoir <NUM> is configured to transition from a contracted or primarily interior configuration (e.g., as illustrated in <FIG>) to a primarily exterior or expanded configuration (e.g., as illustrated in <FIG>), upon addition of fluid into the container <NUM> via the accessor <NUM> or otherwise. As used herein, the term "expanded" is used in its broad and ordinary sense and includes configurations such as those shown in the figures, including deployed, unstored, unfolded, stretched, extended, unrolled, unfurled, or any combination thereof. As used herein, the term "contracted" is used in its broad and ordinary sense and includes configurations such as those shown in the figures, including stored, undeployed, folded, compacted, unstretched, unextended, rolled, furled, or any combination thereof. As shown in the drawings, "expanded" or "contracted," or variants of these words, or similar terms, do not require complete or total expansion or contraction to the fullest possible degree.

In some embodiments, the reservoir <NUM> is contained entirely within the regulator <NUM> when the reservoir <NUM> is in the contracted configuration. In some such embodiments, a cap or other enclosing structure can confine the reservoir <NUM> within the regulator <NUM>. In some embodiments, the reservoir <NUM> is partially enclosed within the regulator <NUM>. The enclosing structure and/or regulator <NUM> can limit or prevent access to (e.g., physical contact with) the reservoir <NUM> when the reservoir <NUM> is in the contracted configuration.

In some embodiments, the volume of the reservoir <NUM> in the contracted configuration is substantially smaller than the volume of the container <NUM>. For example, the volume of the contracted reservoir <NUM> can be less than or equal to about <NUM>% of the volume within the container <NUM> and/or greater than or equal to about <NUM>% of the volume within the container <NUM>. In some embodiments, the volume of the contracted reservoir <NUM> is approximately <NUM>% of the volume of the container <NUM>. The volume of the portion of the regulator <NUM> in which the contracted reservoir <NUM> is contained can be approximately equal to the volume of the contracted reservoir <NUM>. In some embodiments, the volume of the portion of the regulator <NUM> in which the contracted reservoir <NUM> is contained is greater than or equal to about <NUM>% of the volume of the contracted reservoir <NUM> and/or less than about <NUM>% of the volume of the contracted reservoir <NUM>.

At least a portion of the reservoir <NUM> can expand outside of the regulator <NUM> when the reservoir <NUM> transitions to the expanded configuration. In some embodiments, as illustrated, substantially all of the volume-enclosing region of the reservoir <NUM> can move to the exterior of the regulator <NUM> in the primarily exterior position. The volume of the reservoir <NUM> in this configuration can be substantially greater than the volume of the reservoir <NUM> in the contracted configuration. For example, the volume of the reservoir <NUM> in the expanded configuration can be greater than or equal to about <NUM>% of the volume of the container <NUM> and/or less than about <NUM>% of the volume of the container <NUM>. In some embodiments, the volume of the expanded reservoir <NUM> is approximately <NUM>% of the volume of the container <NUM>. Many variations are possible.

<FIG> illustrate an embodiment of a vial adaptor <NUM>. The vial adaptor <NUM> can include a connector interface <NUM>. The connector interface <NUM> can be configured to facilitate coupling the vial adaptor <NUM> with a medical connector (not shown) (e.g., a luer connector or other medical connector), another medical device (not shown), or any other instrument used in extracting fluid from or injecting fluid into a vial (not shown). The vial adaptor <NUM> can be configured to inhibit or prevent release of vapors or other harmful materials from the vial when the vial adaptor <NUM> is coupled with the vial.

The vial adaptor <NUM> can include a body portion <NUM>. The body portion <NUM> can include a central portion <NUM>. In some embodiments, the central portion <NUM> is curved. In some embodiments, the body portion includes one or more legs <NUM> (e.g., which can be opposing). Each or either of the legs <NUM> can be supported at a proximal end of the leg <NUM> by the central portion <NUM> of the body portion <NUM>. In some embodiments, the distal ends of the legs <NUM> are unrestrained to allow the legs <NUM> to deflect. The body portion <NUM> can be removably secured to a vial (not shown). In some embodiments, the body portion <NUM> includes only a single tab, the single tab configured to removably secure the vial adaptor <NUM> to the outside surface of the vial and to facilitate the removal of the vial adaptor <NUM> from the vial.

The vial adaptor <NUM> can include a piercing member <NUM>. The piercing member <NUM> can be supported by the body portion <NUM>. The piercing member <NUM> can project distally from the central portion <NUM> of the body portion <NUM>. In some embodiments, the piercing member <NUM> includes an access channel <NUM> and a regulator channel <NUM>. In some embodiments, the regulator channel <NUM> begins at a distal regulator aperture 128a, passes generally through the piercing member <NUM>, passes through a lumen <NUM> that extends radially outward from the connector interface <NUM>, and terminates at a proximal regulator aperture <NUM>. In some embodiments, the lumen <NUM> extends radially outward from the connector interface <NUM> in only one direction. In some embodiments, the lumen <NUM> extends radially outward from the connector interface <NUM> in more than one direction (e.g., in two opposing directions). For example, the lumen <NUM> can extend through the connector interface <NUM> to a second lumen <NUM>. Some of the views shown in <FIG>, including <FIG>, <FIG>, and <FIG>, do not include an illustration of the flexible enclosure <NUM> positioned in the storage chamber <NUM> of the adaptor <NUM>, even though the flexible enclosure <NUM> is stored in the chamber <NUM>, as shown in <FIG>.

In some embodiments, the regulator assembly <NUM> includes a regulator base configured to couple (e.g., releasably couple or fixedly couple) with a regulator nest <NUM>. The regulator base <NUM> can be constructed from a rigid or semi-rigid material. In some embodiments, the regulator base <NUM> is constructed from a polymer (e.g., a polycarbonate plastic). The regulator base <NUM> can include a coupling protrusion 185a. In some embodiments, the coupling protrusion 185a defines a coupling passage <NUM> (e.g., a regulator assembly channel). The coupling protrusion 185a can be configured to couple with the lumen <NUM> of the vial adaptor <NUM>. For example, the coupling protrusion 185a has an outer cross-sectional shape (e.g., a circle, oval, polygon, or other shape) sized and shaped to generally match an interior cross-section of a lumen <NUM> of the vial adaptor <NUM>. In some embodiments, the coupling protrusion 185a can be configured to friction-fit into the lumen <NUM>. In some embodiments, one or more attachments are used, such as one or more sonic welds, glues, or adhesives, to affix the coupling protrusion 185a to the lumen <NUM>. As illustrated in <FIG>, coupling passage <NUM> can be in fluid communication with the regulator channel <NUM> of the vial adaptor <NUM> when the coupling protrusion 185a is coupled with or otherwise associated with the lumen <NUM>. For example, the coupling protrusion 185a may be coupled with a proximal passageway (e.g., proximal regulator passageway) defined by a portion of the regulator channel <NUM> between the valve <NUM> and the proximal end of the lumen <NUM>. In some embodiments, the regulator assembly <NUM> does not include a valve in the regulator channel <NUM> or in the lumen <NUM>.

As illustrated in <FIG>, the regulator base <NUM> can include a base protrusion <NUM> that extends from the regulator base <NUM> in a direction generally opposite from the direction in which the coupling protrusion 185a extends. The base protrusion <NUM> can have an outer width (e.g. an outer diameter) D4. An inner wall of the base protrusion <NUM> can comprise a portion of the coupling passage <NUM>. The regulator base <NUM>, in some embodiments, can include an axial projection <NUM>. The axial projection <NUM> can extend from the regulator base <NUM> in the same direction as the base protrusion <NUM>. The axial projection <NUM> can, in some embodiments, have a generally annular shape. In some embodiments, the axial projection <NUM> has a generally oval shape, generally polygonal shape, generally circular shape, or any other appropriate shape.

In some embodiments, a filter cavity <NUM> (e.g., filter chamber) can be positioned in a space between the base protrusion <NUM> and the axial projection <NUM> (e.g., surrounding a portion of the lumen <NUM>). The inner width of the filter cavity <NUM> can be the width D4 of the base protrusion <NUM> (e.g., the inner wall of the filter cavity <NUM> can have a width D4). The outer width D9 of the filter cavity <NUM> can be the inner width of the axial projection <NUM> (e.g., the outer wall of the filter cavity <NUM> can have a width substantially equal to the width of the axial projection <NUM>). In some embodiments, the filter cavity <NUM> has a generally toroidal shape. The word "toroidal" is used herein in its broad and ordinary sense and includes, for example, toroidal shapes (e.g., tori, rectangular toroids, polygonal toroids), irregular toroidal shapes (e.g., toroids with protrusions, non-circular shapes, notches, cutouts, etc.), or any combination thereof. In some embodiments, the filter cavity <NUM> has a generally square, generally rectangular, generally triangular, generally oval shape, or other shape.

A filter <NUM> can be sized to fit within the filter cavity <NUM>. The filter <NUM> can have an inner width (e.g., diameter) D5 configured to be less than or equal to about the inner width D4 of the filter cavity <NUM>. In some embodiments, the inner width D5 of the filter <NUM> is greater than the inner width D4 of the filter cavity <NUM>. In some embodiments, the filter <NUM> has an outer width (e.g., diameter) D6 that is greater than or equal to about the outer width D9 of the filter cavity <NUM>. The filter <NUM> can be a hydrophobic and/or an antibacterial filter. In some embodiments, the filter <NUM> is constructed from a paper, polymer, foam, or other material, such as a light-weight porous material. In some embodiments, the filter <NUM> is constructed from a flexible or semi-flexible material. The filter <NUM> can be configured to deform when inserted into the filter cavity <NUM>. For example, the inner width D5 of the filter <NUM> can fit snugly onto or stretch onto the width D4 of the base protrusion <NUM>. In some embodiments, the outer width D6 of the filter <NUM> fits snugly against or is compressed into the outer width D9 of the filter cavity <NUM>. In some embodiments, a snug fit between the filter <NUM> and the filter cavity <NUM> can inhibit fluid from flowing into and/or out of the filter cavity <NUM> and/or coupling channel <NUM> without going through the filter <NUM>.

The regulator assembly <NUM> can include a diaphragm <NUM>. The diaphragm <NUM> can, in some embodiments, have a generally circular or generally annular shape (e.g., a generally toroidal shape, as illustrated). In some embodiments, the shape of the diaphragm <NUM> is configured to generally match the shape of the axial projection <NUM> of the regulator base <NUM>. The diaphragm <NUM> can be inserted into or onto the base portion <NUM>. For example, a lip 163b of the diaphragm <NUM> can be configured to fit around the radial (e.g., up and down in <FIG>) outside of the axial projection <NUM>. The diaphragm <NUM> can include an inner aperture 163a (e.g., an orifice defined by an inner perimeter, as illustrated) having a width (e.g., a diameter) D3. For example, the inner aperture 163a may have a generally circular shape. In some embodiments, as illustrated, the width D3 can be less than the outer width D4 of the base protrusion <NUM>. In some embodiments, as illustrated, the diaphragm <NUM> is positioned generally coaxially with the base protrusion <NUM>. In some embodiments, the diaphragm <NUM> is positioned generally coaxially with the coupling passage <NUM>, as illustrated. In some embodiments, as illustrated, the inner aperture 163a (e.g., orifice or inner orifice) of the diaphragm <NUM> comprises a portion of the regulator assembly channel <NUM>.

The regulator nest <NUM> can be configured to releasably or otherwise couple with the regulator base <NUM>. As illustrated in <FIG>, the regulator nest <NUM> can include one or more fixation members <NUM>. The fixation members <NUM> can be constructed and/or configured to engage with fixation apertures <NUM> on the regulator base <NUM>. The fixation members <NUM> can comprise clips, tabs, or other projections configured to insert into the fixation apertures <NUM> of the regulator base <NUM>. For example, the fixation members <NUM> can comprise a tab 192a with a hook 192b on the end. The fixation members <NUM> can be constructed from a resilient material. For example, tabs 192a of the fixation members <NUM> can be configured to deform (e.g., deflect) or otherwise move when a radial (e.g., up and down with respect to <FIG>) force is applied to the hooks 192b. The regulator base <NUM> can include angled tabs 134a configured to deflect the hooks 192b radially (e.g., up and down with respect to <FIG>) outward as the tabs 192a are inserted into the apertures <NUM>. The hooks 192b can snap back in place upon passing through the fixation apertures <NUM> and can engage with the rear side (e.g., the side away from the regulator nest <NUM>) of the angled tabs 134a to secure the regulator nest <NUM> to the regulator base <NUM>.

As illustrated in <FIG>, the regulator nest <NUM> can include an axial projection <NUM>. The axial projection <NUM> can extend from the regulator nest <NUM> toward the regulator base <NUM> when the regulator nest <NUM> is coupled with the regulator base <NUM>. The axial projection <NUM> can, in some embodiments, have a generally annular shape. In some embodiments, the axial projection <NUM> has a generally oval shape, a generally polygonal shape, a generally circular shape, or any other appropriate shape. The shape of the axial projection <NUM> can be similar to or the same as the shape of the axial projection <NUM> of the regulator base <NUM>. As illustrated, the axial projection <NUM> can contact at least a portion of the diaphragm <NUM> as the regulator nest <NUM> is coupled with the regulator base <NUM>. In some embodiments, contact between the axial projection <NUM> of the regulator nest <NUM> and the diaphragm <NUM> can secure at least a portion of the diaphragm <NUM> in position between the axial projection <NUM> and the axial projection <NUM> of the regulator base <NUM>. For example, the axial projections <NUM>, <NUM> can secure in position a portion of the diaphragm <NUM> adjacent to or near the lip 163b.

As illustrated, in some embodiments the base protrusion <NUM> can extend further than the axial projection <NUM> in the direction away from the coupling protrusion 185a. In some embodiments, a portion of the diaphragm <NUM> adjacent the inner aperture 163a can be deflected or otherwise moved away from the coupling protrusion 185a when the regulator nest <NUM> is coupled to the regulator base <NUM>. Deflection of the portion of the diaphragm <NUM> adjacent the inner aperture 163a can create a biasing force (e.g., a return force within the material of the diaphragm <NUM>) that can bias the inner aperture 163a of the diaphragm <NUM> toward a lip <NUM> (e.g., the end of the base protrusion <NUM> furthest from the regulator base <NUM>, as illustrated in <FIG>) of the base protrusion <NUM>. The lip <NUM> of the base protrusion <NUM> can be formed with a configuration to help produce a low amount of interface or surface area of contact on its forward edge (such as an angled or beveled configuration). For example, a valve seat <NUM> can be formed on or near the radially (e.g., up and down with respect to <FIG>) outward portion of the base protrusion <NUM>. Engagement between the diaphragm <NUM> and the valve seat <NUM> can form a one-way diaphragm valve (e.g., a diaphragm check valve or intake valve, as illustrated) as will be described in more detail below. The valve seat <NUM> can be located further from the coupling protrusion 185a than a radially (e.g., up and down with respect to <FIG>) inward portion of the lip <NUM>. In some embodiments, a beveled lip can inhibit or prevent the diaphragm <NUM> from sticking to the valve seat <NUM> by producing a low amount of surface area contact or interface between the diaphragm <NUM> and the valve seat <NUM>.

In some embodiments, the vial adaptor <NUM> includes an expansion inhibitor, such as an enclosure cover <NUM>. The expansion inhibitor can inhibitor or resist or prevent the expansion or movement of the flexible enclosure <NUM> within or away from the regulator nest. In some embodiments, the enclosure cover <NUM> is configured to cover or obscure or retain all of a flexible enclosure <NUM> within the regulator assembly <NUM> or to cover or obscure or retain all of the flexible enclosure <NUM> and a front region of the regulator assembly <NUM>. In some embodiments, the expansion inhibitor or enclosure cover <NUM> does not cover or obscure or retain all of the flexible enclosure <NUM>. The enclosure cover <NUM> can be constructed from a resilient, flexible, or semi-flexible material. For example, the enclosure cover <NUM> can be constructed from rubber, silicone, and/or some other flexible or semi-flexible material. The enclosure cover <NUM> can be sized and shaped to fit around the radially (e.g., up and down with respect to <FIG>) outward portion of the regulator nest <NUM>. For example, as illustrated in <FIG>, the enclosure cover <NUM> can include an inner lip 198a configured to wrap around one axial side (e.g., the axial side of the regulator nest <NUM> closest to the regulator base <NUM> in the assembled regulator assembly <NUM>) of the regulator nest <NUM> and an outer lip 198b configured to wrap around the other axial side of the regulator nest <NUM>. As illustrated, the inner lip 198a can be about the same thickness as or thicker than the outer lip 198b. In some embodiments, the inner lip 198a of the regulator enclosure cover <NUM> can be positioned or wedged between the regulator nest <NUM> and the regulator base <NUM> when the regulator nest <NUM> is coupled with the regulator base <NUM>. In some embodiments, wedging the inner lip 198a of the enclosure cover <NUM> can inhibit or prevent the enclosure cover <NUM> from detaching from the regulator nest <NUM>. In some embodiments, adhesives can be used to adhere the enclosure cover <NUM> to the regulator nest <NUM>. The outer lip 198b of the enclosure cover <NUM> can include or define an expansion aperture <NUM>. For example, the outer lip 198b can define a circular or otherwise shaped opening to define the expansion aperture <NUM>. The expansion aperture <NUM> can have a width WS4 that is less than a width WS3 of the regulator nest <NUM>.

As illustrated in <FIG>, the vial adaptor <NUM> can include a flexible enclosure <NUM>. The flexible enclosure <NUM> can be configured to fit within a storage chamber <NUM> within the regulator nest <NUM> and/or the enclosure cover <NUM>. In some embodiments, the flexible enclosure <NUM> is folded into the storage chamber <NUM> when the flexible enclosure <NUM> is in a contracted configuration. In some embodiments, as illustrated, the flexible enclosure <NUM> is not generally expandable by stretching the material of the flexible enclosure <NUM> in the plane of such material, to avoid creating an opposing pressure against the expansion which would tend to encourage gas within the flexible enclosure <NUM> to be urged back out of the flexible enclosure <NUM>. Rather, by primarily unfolding instead of primarily stretching the flexible enclosure <NUM> to increase its volume, the gas inside of the flexible enclosure <NUM> is not generally urged back out of the flexible enclosure <NUM> unless and until one or more other forces in the system act upon it to do so. The flexible enclosure <NUM> can be connected to the regulator nest <NUM> at an attachment point <NUM>. For example, an adhesive (e.g., glue, tape, foam tape or other appropriate adhesive) can be used to attach an opening of the flexible enclosure <NUM> to the regulator nest <NUM>. The flexible enclosure <NUM> can be connected and/or coupled with the regulator nest <NUM> in a fluid tight fashion. For example, the flexible enclosure <NUM> can define an inner volume VE1, VE2 in communication with the coupling passage <NUM> of the regulator base <NUM>. In some embodiments, the interior volume VE1, VE2 of the flexible enclosure <NUM> is not in fluid communication with ambient when the diaphragm check valve is in the closed position.

In some embodiments, as illustrated in <FIG>, the regulator assembly <NUM> can include one or more intake ports <NUM>. The intake ports <NUM> can be positioned along or near the coupling protrusion 185a. In some embodiments, the intake ports <NUM> are positioned in a wall of the regulator base <NUM> away from the coupling protrusion 185a. One or more spacers 144a can be located adjacent to the intake ports <NUM>. The spacers 144a can be configured to limit the extent to which the coupling protrusion 185a enters into the lumen <NUM> when the regulator base <NUM> is coupled with the lumen <NUM>. In some embodiments, the spacers 144a inhibit or prevent intake ports <NUM> from being blocked by the regulator base <NUM> and/or the lumen <NUM>.

As illustrated in <FIG>, the intake ports <NUM> can facilitate communication between ambient and the filter <NUM>. In some embodiments, upon withdrawal of fluid from a vial onto which the vial adaptor <NUM> is attached, a pressure deficit can be realized in the coupling passage <NUM>. A reduction in pressure in the coupling passage <NUM> can create a pressure differential at the interface between the valve seat <NUM> and the diaphragm <NUM>. In some embodiments, the diaphragm <NUM> is configured to deflect or otherwise move away from the valve seat <NUM> when a predetermined pressure differential (e.g., a pressure differential wherein the pressure in the coupling passage <NUM> is lower than the ambient pressure) is applied across the diaphragm <NUM>. As shown in <FIG>, deflection or other movement of the diaphragm <NUM> away from the valve seat <NUM> (e.g., transition of the diaphragm or intake valve to the opened configuration, as illustrated) can facilitate fluid communication between ambient and the coupling passage <NUM> (e.g., fluid flow into the interior of the regulator assembly <NUM> between the valve seat <NUM> and the inner perimeter of the valve member <NUM> comprising the inner aperture 163a, as illustrated). In some embodiments, fluid communication between ambient and the coupling passage <NUM> can help to equalize the pressure between the interior of the vial <NUM> and ambient. Fluid passing from ambient to the coupling passage <NUM> can pass through the filter <NUM>. In some embodiments, the filter <NUM> can inhibit or prevent introduction of contaminants (e.g., bacteria, viruses, particulates) into the coupling passage <NUM> when the diaphragm check valve is open (e.g., when the diaphragm <NUM> is disengaged from the valve seat <NUM>). The diaphragm <NUM> can be configured to return to its engagement with the valve seat <NUM> (e.g., the closed configuration of the diaphragm or intake valve) when a predetermined pressure differential (e.g., generally equal pressure, or some other pressure differential) occurs between the interior of the vial (e.g., the coupling passage <NUM>) and ambient.

In some embodiments, a health care practitioner may withdraw fluid from the vial <NUM> in a vented manner via the access channel <NUM> after coupling the vial adaptor <NUM> with the vial <NUM> both prior to and after injecting fluid into the vial <NUM> via the access channel <NUM>. For example, a diaphragm check valve formed by the diaphragm <NUM> and the valve seat <NUM> can permit fluid withdrawal from the vial <NUM> via the access channel <NUM> in a vented manner (e.g., in a manner that maintains a pre-determined pressure range within the vial <NUM> during withdrawal of fluid) prior to expansion of the flexible enclosure <NUM> by permitting fluid ingress through the intake ports <NUM> through the filter <NUM>. In some embodiments, the gas pressure within the vial is maintained at a generally equal level with ambient air pressure so that fluid within a withdrawing medical implement (such as a syringe connected to the vial adapter) is not unintentionally drawn back into the vial and so that the risk of microspraying, gas release, or other undesirable occurrences during connection or disconnection are substantially reduced or eliminated.

In some embodiments, upon introduction of fluid into the vial <NUM> via the access channel <NUM>, an increase in pressure can be realized within the coupling passage <NUM>. The volume within the flexible enclosure <NUM> can be configured to expand in response to an increase in pressure within the coupling passage <NUM> to a desirable or predetermined pressure. For example, upon introduction of fluid into the vial via the access channel <NUM>, the pressure in the coupling channel <NUM> can increase to a point that the volume within the flexible enclosure <NUM> expands to the expanding configuration, as illustrated in <FIG>. In the expanded configuration, the flexible enclosure can have a width (e.g., a diameter) D7 (e. g, an expanded width or deployed width). The width D7 of the flexible enclosure <NUM> can be greater than a width (e.g., a diameter) D11 of the regulator nest <NUM>. For example, the width D7 can be greater than or equal to about <NUM>% of the width D11 and/or less than or equal to about <NUM>% of the width D11. In some embodiments, the width D7 of the expanded flexible enclosure <NUM> is approximately <NUM>% of the width D11 of the regulator nest <NUM>. As shown in the example illustrated in <FIG>, the width D11 of the regulator nest <NUM> can be about the same as or less than the distance between the proximal end of the connector interface <NUM> and the distal end of the piercing member <NUM>, and/or the width D11 of the regulator nest <NUM> can be about the same as or less than the distance between the proximal end of the connector interface <NUM> and the distal end of a connection portion <NUM> of the vial adaptor <NUM> that is adapted to grasp a portion of the vial, and/or the width D11 of the regulator nest <NUM> can be less than a distance between the connector interface <NUM> and the distal regulator aperture 128a. The expanded volume VE4 of the flexible enclosure <NUM> can be greater than the storage chamber volume VS of the storage chamber <NUM>. For example, the expanded volume DE4 of the flexible enclosure <NUM> can be greater than or equal to about <NUM>% of the volume VS of the storage chamber <NUM> and/or less than or equal to about <NUM>,<NUM>% of the volume VS of the storage chamber <NUM>. In some embodiments, the expanded volume VE4 of the expanded flexible enclosure <NUM> is greater than or equal to about <NUM>,<NUM>% of the volume VS of the storage chamber <NUM> and/or less than or equal to about <NUM>,<NUM>% of the volume VS of the storage chamber <NUM>. In some embodiments, the expanded volume VE4 of the expanded flexible enclosure <NUM> is approximately about <NUM>,<NUM>% of the volume VS of the storage chamber <NUM>. Many variations are possible.

The volume within the flexible enclosure <NUM>, after transition to the expanded configuration, can be configured to contract to the contracted configuration upon withdrawal of fluid from the vial <NUM> via the access channel <NUM>. Contraction of the volume within the flexible enclosure <NUM> can facilitate introduction of regulator fluid from the interior volume of the flexible enclosure <NUM> to the vial <NUM> via the regulator channel <NUM>. (e.g., through the proximal regulator passageway and through a distal passageway of the regulator channel <NUM> between the valve <NUM> and the distal regulator aperture 128a, as illustrated). Introduction of regulator fluid from the interior volume of the flexible enclosure <NUM> to the vial <NUM> can facilitate maintenance of the pressure within the vial <NUM> within a desirable or predetermined range.

As illustrated in <FIG>, a radial (e.g., with respect to the centerline CL of the piercing member <NUM>) distance DS3 between the regulator base <NUM> and the center line of the vial adaptor <NUM> can be greater than the radial distance DS4 between the radially inner edge of the regulator base <NUM> and the radially outward edge of the enclosure cover <NUM>. In some embodiments, the radial distance DS3 is greater than or equal to <NUM>% of the radial distance DS4 and/or less than or equal to <NUM>% of the radial distance DS4. In some embodiments, the radial distance DS3 is approximately <NUM>% of the radial distance DS4.

In some embodiments, the flexible enclosure <NUM> is folded and stored within the storage chamber <NUM> when the flexible enclosure <NUM> is in the contracted configuration. In some embodiments, the flexible enclosure <NUM> is folded into a polygonal shape, circular shape, and/or oval shape before being stored in the storage chamber <NUM>. For example, as illustrated in <FIG>, the flexible enclosure <NUM> can be folded into a substantially rectangular shape within the storage chamber <NUM>.

As discussed above, the flexible enclosure <NUM> can be configured to transition to an expanded configuration upon introduction of fluid into the vial <NUM> via the access channel <NUM>. In some embodiments, the flexible enclosure <NUM> is folded and stored within the storage chamber <NUM> such that at least a portion of the flexible enclosure <NUM> realizes a frictional resistance with a portion of the outer lip 198b of the enclosure cover <NUM> as the flexible enclosure <NUM> transitions to the expanded configuration from the contracted configuration. Frictional resistance between the folded flexible enclosure <NUM> and the outer lip 198b can inhibit or prevent the flexible enclosure <NUM> from rapidly transitioning to the expanded configuration. Slowing the transition of the flexible enclosure <NUM> from the contracted configuration to the expanded configuration can inhibit or prevent the check valve <NUM> from accidentally closing and can generally help diminish stresses within the system of the vial, the vial adaptor, and the medical implement (e.g., syringe) to which vial is being transferred, that may otherwise increase the risk of leaking or other failures.

In some embodiments, the flexible enclosure <NUM> is configured to unfold from the contracted configuration in a consistent and/or controlled manner in order to promote a consistent, slow, and predictable expansion of the volume within the flexible enclosure <NUM>. For example, the flexible enclosure <NUM> can be folded in a desirable or predetermined pattern (e.g., the patterns disclosed in <FIG> and described below) and unfolded in a desirable or predetermined pattern (e.g., the folds made in the folding pattern unfold in the reverse order from the order in which they were folded).

In some embodiments, the flexible enclosure <NUM> is folded into the storage chamber <NUM> such that the folds of the flexible enclosure <NUM> form a generally laminate substrate of enclosure layers. For example, as illustrated in <FIG>, a plurality of flexible enclosure layers can be positioned between a nest aperture <NUM> of the regulator nest <NUM> and the expansion aperture <NUM> of the outer lip 198b of the enclosure cover <NUM>. In some embodiments, the flexible enclosure layers can substantially reduce, minimize, or eliminate the likelihood of material failure (e.g., puncture, tearing, rupture) of the flexible enclosure <NUM> from impact or other external forces on the layer of the folded flexible enclosure <NUM> closest to the expansion aperture <NUM> (e.g., the layer of the folded flexible enclosure <NUM> most exposed to ambient when the flexible enclosure <NUM> is in the contracted configuration). For example, the laminate configuration of the folds of the folded flexible enclosure <NUM> can increase the effective thickness (e.g., the sum thickness of the laminate layers) of the flexible enclosure <NUM> layers with respect to impact or other forces applied from the exterior of the regulator assembly <NUM>. In some embodiments, the laminate configuration of the folded flexible enclosure <NUM> can reduce, minimize, or eliminate any likelihood that the flexible enclosure <NUM> would rupture due to increased pressure from within the vial <NUM>. For example, as described above, the laminate layers can increase the effective thickness of the flexible enclosure <NUM> with respect to pressure within the vial <NUM>.

As illustrated in <FIG>, the flexible enclosure <NUM> can have a very small internal volume VE3 when in the contracted configuration. For example, folding the flexible enclosure <NUM> (e.g., according to the processes described below) can diminish the space between the laminate folded layers of the folded flexible enclosure <NUM> and can eject much or most of the fluid from within the flexible enclosure <NUM>. In some embodiments, ejecting much or most of the fluid from the folded flexible enclosure <NUM> can increase the volume difference between the contracted flexible enclosure <NUM> (e.g., a shown in <FIG>) and the expanded flexible enclosure <NUM> (e.g., as shown in <FIG>). In some embodiments, increasing the volume difference between the contracted flexible enclosure <NUM> and the expanded flexible enclosure <NUM> can reduce, minimize, or eliminate any need to use a stretchable material for the flexible enclosure <NUM>. For example, a flexible material with little or no stretchability (e.g. Mylar® film ) can be used to construct the flexible enclosure <NUM>. In some embodiments, the flexible enclosure <NUM> is constructed from polyethylene or some other appropriate material.

<FIG> illustrate an embodiment of a vial adaptor <NUM> that can have components or portions that are the same as or similar to the components or portions of other vial adaptors disclosed herein. In some embodiments, the vial adaptor <NUM> includes a connector interface <NUM> and a piercing member <NUM> in partial communication with the connector interface <NUM>. In some embodiments, the vial adaptor <NUM> includes a regulator assembly <NUM>. Some numerical references to components in <FIG> are the same as or similar to those previously described for the vial adaptor <NUM> (e.g., piercing member <NUM> v. piercing member <NUM>). It is to be understood that the components can be the same in function or are similar in function to previously-described components. The adaptor <NUM> of <FIG> shows certain variations to the adaptor <NUM> of <FIG>.

As illustrated, the filter <NUM> of the regulator assembly <NUM> can be a thin filter (e.g., substantially thinner than the diameter or cross-section of the filter <NUM>). The filter <NUM> can be hydrophobic and/or antimicrobial. In some embodiments, the filter <NUM> is configured to engage with a first filter seat 233a and a second filter seat 264a. One or both of the first filter seat 233a and the second filter seat 264a can be an annular ridge. For example, the first filter seat 233a can be an annular ridge positioned on a stepped portion of the base protrusion <NUM> of the regulator base <NUM>. The second filter seat 264a can be, for example, an annular ridge positioned on a stepped portion of the regulator base <NUM>. In some embodiments, the filter <NUM> is affixed to the first filter seat 233a and/or to the second filter seat 264a via an adhesive of other appropriate fixation compound or technique.

The diaphragm <NUM> can be fixed between the regulator nest <NUM> and the regulator base <NUM>. In some embodiments, the lip 263b of the diaphragm <NUM> can be positioned or wedged between the axial projection <NUM> of the regulator nest <NUM> and a base ridge 264b. The base ridge 264b can be a generally annular ridge. The lip 263b of and/or the entire diaphragm <NUM> can be constructed from a flexible and/or compressible material. In some embodiments, wedged engagement between the lip 263b of the diaphragm <NUM> and the base ridge 264b can reduce, minimize, or eliminate the possibility that fluid will unintentionally bypass the diaphragm <NUM> around the lip 263b.

<FIG> illustrate an example of a folded flexible enclosure <NUM> and an example of a method of folding the flexible enclosure <NUM>. In some embodiments, the flexible enclosure <NUM> can be defined in multiple (e.g., three) horizontal (e.g., left to right with reference to <FIG>) portions that have relatively equal horizontal extents. The multiple horizontal portions can be separated by multiple fold lines FL1 and FL2. The method of folding the flexible enclosure <NUM> can include folding a first portion or quadrant Q1 of the flexible enclosure <NUM> along the fold line FL1. The method can include folding a second portion or quadrant Q2 over the first portion or quadrant Q1 generally along the fold line FL2. As illustrated in 40B, a method of folding the flexible enclosure <NUM> can include dividing the flexible enclosure <NUM> into multiple (e.g., three) vertical portions (e.g., up and down with respect to <FIG>). The multiple vertical portions can be separated by another (e.g., a third) fold line FL3 and yet another (e.g., a fourth) fold line FL4. A method of folding the flexible enclosure <NUM> can include folding another (e.g., a third) portion or quadrant along fold line FL3. Yet another portion (e.g., a fourth) or quadrant Q4 can be folded over the previously formed (e.g., third) portion or quadrant Q3 along fold line FL4. Upon folding quadrant <NUM> over quadrant <NUM>, as illustrated in Figure 40B, the flexible enclosure can have a generally square or rectangular shape. The square or rectangle of the flexible enclosure <NUM> can have a major diagonal line D8. (e.g., a stored or contracted width). The major diagonal line D8 can be less than or about equal to a width WS3 of the regulator nest <NUM> (e.g., the storage chamber width). As illustrated in Figure 40B, the diagonal line D8 can be greater than or about equal to the width WS4 of the expansion aperture <NUM>.

<FIG> illustrate a method of folding the flexible enclosure <NUM>. The fold lines of the method illustrated in <FIG> can generally form a square having a diagonal approximately equal to the width D7 of the expanded flexible enclosure <NUM>. The method can include folding a first quadrant Q1a of the flexible enclosure <NUM> toward the second quadrant Q2a (e.g., the quadrant on the generally opposite side of the flexible enclosure <NUM> from the quadrant Q1a) along the first fold line FL1a. The first quadrant Q1a can then be folded back toward the fold line FL1a. In some embodiments, the second quadrant Q2a is folded over the first quadrant Q1a along the second fold line FL2a. The second quadrant Q2a can then be folded back toward the fold line FL2a. The third quadrant Q3a may be folded toward the fourth quadrant Q4a along the third fold line FL3a. According to some configurations, the fourth quadrant Q4a is then folded over the third quadrant Q3a along the fourth fold line FL4a. The generally stacked or laminated third and fourth quadrants Q3a, Q4a then can be folded along the fifth fold line FL5 to form a substantially rectangular folded flexible enclosure <NUM> having a diagonal D12. The length of diagonal D12 can be greater than the width WS4 of the expansion aperture <NUM> and/or less than or equal to about the width WS3 of the regulator nest <NUM>.

<FIG> illustrate embodiments of a regulator assembly <NUM>. As with all embodiments in this specification, any structure, feature, material, or step that is illustrated or described in connection with <FIG> can be used with or instead of any structure, feature, material, or step that is illustrated or described in any other embodiment in this specification. The vial adaptors and regulator assemblies described in <CIT> (now published as <CIT>), <CIT> and issued September <NUM>, <NUM>, <CIT> (now published as <CIT>), and <CIT>.

Any structure, feature, material, or step that is illustrated or described in connection with any embodiment of the foregoing patent applications can be used with or instead of any structure, feature, material, or step that is illustrated or described in any other embodiment in this specification. In some embodiments, the regulator assembly <NUM> includes a regulator base <NUM> and a regulator nest <NUM> configured to fixedly or removably couple with the regulator base <NUM>. Some numerical references to components in <FIG> are the same as or similar to those previously described for the regulator assemblies <NUM> and <NUM> (e.g., first filter seat 333a v. first filter seat 233a). It is to be understood that the components can be the same in function or are similar in function to previously-described components. For example, the coupling protrusion 385a of the regulator base <NUM> can be configured to couple with the lumen <NUM> of the body portion <NUM> of <FIG>. For example, the coupling portion 385a can fit within the lumen <NUM> and can be connected to the lumen <NUM> via adhesives, welding, friction-fit, and/or some other connection structure or method. In some embodiments, the coupling portion 385a fits around the exterior of the lumen <NUM> (e.g., the lumen <NUM> fits within the coupling portion 385a). In some embodiments, the regulator assembly <NUM> is used in combination with a check valve positioned in the regulator channel between the distal regulator aperture 128a and the regulator assembly <NUM>. In some embodiments, the regulator assembly <NUM> is used as part of a system without a check valve positioned between the distal regulator aperture and the regulator assembly <NUM> (see, e.g., <FIG>). The regulator assembly <NUM> of <FIG>shows certain variations to the regulator assemblies <NUM> and <NUM> of <FIG>.

As illustrated in <FIG>, the regulator base <NUM> can include an annular wall <NUM>. The annular wall <NUM> can extend around an outer perimeter of the regulator base <NUM> (e.g., with respect to a regulator axis <NUM> of the regulator assembly <NUM>). In some embodiments, the annular wall <NUM> extends away from the coupling protrusion 385a in a direction parallel or approximately parallel to the regulator axis <NUM>. For example, the annular wall <NUM> can extend beyond the regulator nest <NUM> when the regulator nest <NUM> is coupled with the regulator base <NUM> (see, e.g., <FIG> and <FIG>). In some embodiments, extending the annular wall <NUM> beyond the nest <NUM> can permit attachment of a cover <NUM> or cap 380a to the annular wall <NUM>, as described below. Connecting the cover/cap <NUM>/380a to the annular wall <NUM> can reduce a risk that the regulator nest <NUM> and regulator base <NUM> decouple during removal of the cover/cap. The annular wall <NUM> can define a storage chamber <NUM> in which the flexible enclosure <NUM> can be positioned when in a contracted (e.g., stored) configuration, as illustrated in <FIG>. In some embodiments, as illustrated, the annular wall <NUM> can have a seamless or substantially seamless outer surface (e.g., without protrusions, holes, gaps, or other surface features).

As illustrated in <FIG> and <FIG>, the regulator nest <NUM> can include one or more protrusions, such as a protrusion <NUM>. The protrusion <NUM> can have an annular shape. The protrusion <NUM> can extend from the regulator nest <NUM> toward the regulator base <NUM>. In some embodiments, the protrusion <NUM> is positioned radially (e.g., with respect to the regulator axis <NUM>) outward from the nest aperture <NUM>. In some embodiments, the protrusion <NUM> is positioned radially between the nest aperture <NUM> and the axial projection <NUM>. In some embodiments, the protrusion <NUM> is positioned radially inward from the axial projection <NUM>. The protrusion <NUM> can be sized, shaped, and/or otherwise configured to engage with a portion of the diaphragm <NUM>. For example, the protrusion <NUM> can contact the diaphragm <NUM> between the lip 363b and inner aperture 363a of the diaphragm <NUM>. In some embodiments, the protrusion <NUM> contacts the diaphragm <NUM> when the diaphragm is in a closed position, as illustrated in <FIG>. In some embodiments, the protrusion <NUM> is separated from the diaphragm <NUM> when the diaphragm is in the closed position. The protrusion <NUM> can be configured to bias the diaphragm <NUM> to the closed position. In some embodiments, the protrusion <NUM> increases a cracking pressure of the diaphragm <NUM> (e.g., the pressure differential required to transition the diaphragm from the closed position to an opened position) as compared to an embodiment without the protrusion <NUM>.

The nest aperture <NUM> can have a diameter D13. In some embodiments, the diameter D13 of the nest aperture <NUM> is smaller than the diameter D14 of the coupling protrusion 385a. For example, the diameter D13 of the nest aperture <NUM> can be less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, and/or less than or equal to about ¼, of the diameter D14 of the coupling protrusion 385a. In some embodiments, the diameter D13 of the nest aperture <NUM> is less than or equal to about <NUM>, less than or equal to about <NUM>, less than or equal to about <NUM>, less than or equal to about <NUM>, less than or equal to about <NUM>, and/or less than or equal to about <NUM>. Many variations are possible.

As illustrated in <FIG>, a cover <NUM> can be connected to the regulator assembly <NUM>. For example, the cover <NUM> can be connected to the annular wall <NUM>. The cover <NUM> can be configured to inhibit accidental deployment (e.g., transition from contracted to expanded state of the flexible enclosure <NUM>) or partial deployment (e.g., movement of at least a portion of the flexible enclosure <NUM> from within the nest <NUM> to outside of the nest <NUM>). In some embodiments, the cover <NUM> maintains a uniform, compact profile and appearance to assist in transportation and storage, and reduces the risk of damage to or contamination of the flexible enclosure <NUM> prior to use of the regulator assembly <NUM>.

The cover <NUM> can be liquid and/or gas-impermeable. In some embodiments, the cover <NUM> is constructed from coated paper, silicone, polymer(s), foils, Mylar® film, and/or some other suitable material. In some embodiments, the cover <NUM> is constructed from polyolefin, polyvinyl chloride, polyethylene, polypropylene, and/or a multilayer polymer composition. In some embodiments, the cover <NUM> is constructed from a copolymer such as, for example, ethylene propylene or ethylene vinyl acetate. In some embodiments, the cover <NUM> is constructed from an extruded material, a co-extruded material, a laminate, and/or a biaxially oriented polypropylene. The cover material can be flexible, stretchable, and/or tearable. The cover <NUM> can be transparent, translucent, or opaque.

The cover <NUM> can be removably or temporarily coupled to the regulator assembly <NUM> in any suitable manner, such as adhered, rotated into or onto, screwed into or onto, wrapped, clipped, friction fit, stretched onto, magnetically attached, shrink-wrapped, welded, and/or otherwise attached to the regulator assembly <NUM> (e.g., to an inside and/or outside surface of the annular wall <NUM> of the regulator base <NUM>). In some embodiments, the cover <NUM> includes one or more separable or separating regions configured to easily and predictably produce a separation or split or tear or divide or rupture in the cover when pushed or pulled or influenced by another suitable movement by the user. For example, the one or more separable or separating regions can be one or more perforations or one or more break-away portions. As with all embodiments in this specification, any type of separable or separating region that is illustrated and/or described in this embodiment can be included with or used instead of any structure, feature, material, or step of any other embodiment. For example, as illustrated in <FIG>, the cover <NUM> includes an annular perforation <NUM>. The annular perforation <NUM> can extend around a perimeter of the cover <NUM> near (e.g., within about <NUM>%, within about <NUM>%, or within about <NUM>% of the radius of the cover <NUM>) the outer edge of the cover <NUM>. The annular perforation <NUM> can provide a weakened location on the cover <NUM> configured to be more easily torn and/or punctured than other portions of the cover <NUM>.

As illustrated in <FIG>, the cover <NUM> can include a localized perforation <NUM>. The localized perforation <NUM> can be used in addition to or instead of the annular perforation <NUM>. In some embodiments the localized perforation <NUM> forms, alone or in combination with the annular perforation <NUM>, a localized weakened portion <NUM> of the cover <NUM>. The weakened portion <NUM> of the cover <NUM> can be configured to be removed, punched-through or otherwise moved or oriented or manipulated to facilitate removal of the cover <NUM> from the regulator assembly <NUM> and/or to facilitate uncovering of the flexible enclosure <NUM>, or to create or move or orient a tab to assist in removal of the cover <NUM>. In some embodiments (not shown) a tab or other graspable structure is attached to the weakened portion <NUM> to facilitate pulling and/or tearing of the weakened portion <NUM>.

As illustrated in <FIG> and <FIG>, the cover <NUM> can include a tab <NUM> or other gripping portion. The tab <NUM> can be configured to be grasped by a user of the regulator assembly <NUM>. The tab <NUM> can be configured to facilitate easier removal (e.g., peeling away) of the cover <NUM> from the regulator base <NUM>. In some embodiments, the tab <NUM> is used in addition to or instead of a perforation. In some embodiments, as illustrated, the tab <NUM> extends outward from an outer perimeter of the cover <NUM>. In some embodiments, the tab <NUM> is attached to the cover <NUM> at least partially within the perimeter of the cover <NUM>. The tab <NUM> can be configured to be grasped and pulled in a direction away from the coupling protrusion 385a of the regulator assembly <NUM>.

As illustrated in <FIG>, the regulator assembly <NUM> can include a cap 380a instead of or in addition to a cover <NUM>. The cap 380a can be constructed from any of one or more of the same materials recited above for the cover <NUM>, and/or of one or more different materials. In some embodiments, the cap 380a includes an annular rim <NUM>. The annular rim <NUM> can be sized, shaped, and/or otherwise configured to fit around or inside of a portion of the annular wall <NUM> of the regulator base <NUM>. In some embodiments, the annular wall <NUM> includes one or more mating features (not shown) configured to engage with the annular rim <NUM> of the cap 380a. For example, the annular wall <NUM> can include one or more ridges, ribs, protrusions, detents, channels, indentations, and/or other features configured to facilitate mating with the cap 380a (e.g., with the annular rim <NUM> of the cap 380a. In some embodiments, the cap 380a includes one or more tabs or other structures configured to facilitate gripping of the cap 380a. The cap 380a can be connected to the annular wall <NUM> via friction fit, adhesive, heat-shrinking, and/or some other structure and/or method of connection. The cap 380a can be configured to inhibit accidental deployment (e.g., transition from contracted to expanded) of the flexible enclosure <NUM>. In some embodiments, the cap 380a reduces the risk of damage to the flexible enclosure <NUM> prior to use of the regulator assembly <NUM>.

As illustrated in <FIG>, the regulator assembly (e.g., the regulator base <NUM>) can include one or more intake ports <NUM>. The intake ports <NUM> can function in a manner similar to or the same as the intake ports <NUM> described above. The intake ports <NUM> can have port heights <NUM> (e.g., as measured perpendicular to the regulator axis <NUM>) greater than or equal to about: <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, and/or <NUM>/<NUM> of the diameter D14 of the coupling protrusion 385a.

A method of using the regulator assembly <NUM> can include intentionally removing or modifying the cover <NUM> or cap 380a by a user prior to injection of fluid through the connector interface (e.g., into the vial) or permitting the expanding or moving flexible enclosure <NUM> to automatically remove or modify the cover <NUM> in a manner to permit or facilitate further expansion or movement of the flexible enclosure <NUM>. According to some methods, the cover <NUM> or cap 380a is removed prior to withdrawal of fluid through the connector interface. According to some methods, the cover <NUM> or cap 380a is merely loosened or widened or stretched to permit further expansion or movement of the flexible enclosure <NUM>, but the cover <NUM> or cap 380a essentially remains in place. In some embodiments, the flexible enclosure <NUM> cannot be inflated to a volume beyond that of the storage chamber <NUM> prior to removal of the cover or cap 380a. For example, the cap 380a or cover <NUM> can be configured to prevent expansion of the flexible enclosure <NUM> out of the storage chamber <NUM> under normal operating conditions prior to removal of the cap 380a or cover <NUM> from the regulator assembly <NUM>. In some embodiments, after removal or modification of the cap 380a or cover <NUM>, fluid can be injected through the connector interface <NUM>. Injection of fluid through the connector interface <NUM> into a vial can drive or urge fluid through the regulator channel and into the flexible enclosure <NUM>. The flexible enclosure <NUM> and diaphragm <NUM> can be configured to operate in any of the one or more steps or manners of the flexible enclosures <NUM>, <NUM> and diaphragms <NUM>, <NUM> described elsewhere in this specification (e.g., after the cap or cover 380a, <NUM> is removed). In some embodiments, the cap or cover 380a, <NUM> is configured to be removed only via deliberate user actions such as, for example, pulling of a tab of the cap or cover, tearing of a portion of the cap or cover, and/or otherwise removing the cap or cover from the regulator assembly <NUM>. In some embodiments, the cap or cover 380a, <NUM> is configured to remain in place in the absence of the deliberate user actions described herein (e.g., the cap or cover can be configured to remain connected to the regulator assembly <NUM> in response to injection of fluid into the vial). The action of removing a cover is used herein in its broad and ordinary sense and includes, for example, having a user pull at least a portion of the cover off the adaptor, having a user rip at least a portion of the cover, inflating the flexible enclosure to cause removal of at least a portion of the cover, inflating the flexible enclosure to tear at least a portion of the cover, causing a perforated portion of the cover to separate, and/or any combination of these actions.

<FIG> illustrate embodiments of a regulator assembly <NUM>' that can have components or portions that are the same as or similar to the components or portions of other regulator assemblies disclosed herein. For example, many of the components of the regulator assembly <NUM>' are the same as and have identical reference numbers to those components described above with respect to the regulator assembly <NUM>. As with all embodiments in this specification, any structure, feature, material, or step that is illustrated and/or described in connection with <FIG> can be used with or instead of any structure, feature, material, or step that is illustrated and/or described elsewhere in this specification.

The regulator assembly <NUM>' can utilize a cover 380b. The cover 380b can be configured to wrap around or otherwise cover a substantial portion or a majority of the outer surface area of the regulator base <NUM> and/or regulator nest <NUM>. In some embodiments, the cover 380b includes an annular side portion <NUM> sized and shaped to fit around a radially-outward portion (e.g., with respect to the regulator axis <NUM>) of the regulator base <NUM>. In some embodiments, the side portion <NUM> of the cover 380b is configured to cover an outer surface of the annular wall <NUM> of the regulator base <NUM>.

The regulator base 380b can include a rear flange <NUM>. The rear flange <NUM> can be connected to and/or integral with the side portion <NUM> of the cover 380b. The rear flange <NUM> can wrap around the regulator base <NUM> (e.g., the annular wall <NUM>) on the side of the base <NUM> nearest the coupling protrusion 385a. In some embodiments, the rear flange <NUM> extends radially inward toward the regulator axis <NUM> from the side portion <NUM> of the cover 380b.

As illustrated in <FIG>, the cover 380b can include an aperture <NUM>. The aperture <NUM> can be positioned on a side of the cover 380b opposite the coupling protrusion 385a. The aperture <NUM> can have a width (e.g., diameter) D15. The width D15 of the aperture <NUM> can be less than a width (e.g., diameter) D16 of the regulator assembly <NUM>'. In some embodiments, the width D15 of the aperture <NUM> is less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, less than or equal to about <NUM>/<NUM>, greater than or equal to about <NUM>/<NUM>, greater than or equal to about <NUM>/<NUM>, greater than or equal to about <NUM>/<NUM>, and/or greater than or equal to about <NUM>/<NUM> of the width D16 of the regulator assembly <NUM>'. In some embodiments, the width D15 of the aperture <NUM> is between about <NUM>/<NUM> and about <NUM>/<NUM> of the width D16 of the regulator assembly <NUM>'. In some embodiments, the width D15 of the aperture <NUM> is approximately <NUM>/<NUM> of the width D16 of the regulator assembly <NUM>'. Many variations are possible.

The cover 380b can be constructed from a flexible and/or stretchable material. For example, the cover 380b can be constructed from polyethylene or from some other material. The cover 380b can be constructed from multiple layers. In some embodiments, one or more of the layers of the cover 380b is constructed from a material different from the material of one or more other layers.

The cover 380b can include one or more weakened portions configured to tear at a lower stress than the unweakened portions of the cover 380b. For example, as illustrated in <FIG>, the cover 380b can include one or more perforations <NUM>. In some embodiments, the cover 380b includes only a single perforation <NUM> (see, e.g., <FIG>)). The weakened portions/perforations <NUM> can extend through every layer of the cover 380b or through less than all of the layers of the cover 380b. The weakened portions <NUM> of the cover 380b can be configured to facilitate tearing of the cover 380b during inflation of the flexible enclosure <NUM>. For example, the weakened portions <NUM> can facilitate tearing of the cover 380b to allow for expansion of the flexible enclosure <NUM> out from the cover 380b. The weakened portions <NUM> can be configured to resist tearing during manufacture, assembly, and shipment of the regulator assembly <NUM>'.

In some embodiments, the perforations <NUM> extend from the aperture <NUM> toward the side portion <NUM> of the cover 380b. In some embodiments, the perforations <NUM> extend through the side portion <NUM> and/or through all or part of the rear flange <NUM> of the cover 380b (see, e.g.,.

As illustrated in <FIG>, two or more perforations <NUM> can be positioned close to each other to form one or more pull or break-away perforated segments <NUM>. In some embodiments, the perforated segments <NUM> can be pulled, broken away, moved or modified, and/or torn away from the remainder of the cover 380b prior to or during inflation of the flexible enclosure <NUM>.

A method of using a vial adaptor utilizing the regulator assembly <NUM>' can include connecting the vial adaptor to a vial. This step can include piercing the vial with a piercing member of the vial adaptor. A syringe or other fluid source may be connected to a connector interface of the vial adaptor. Fluid can be injected into the vial via the connector interface and the piercing member. Injection of the fluid into the vial can increase pressure within the vial. Increased pressure within the vial can force fluid through a regulator channel of the regulator assembly <NUM>' into the flexible enclosure <NUM>. The flexible enclosure <NUM> can expand in response to the introduction of fluid from the vial. Expansion of the flexible enclosure <NUM> can stress the cover 380b. Stress of the cover 380b from the expansion of the flexible enclosure <NUM> can facilitate tearing of one or more of the perforations <NUM>. Tearing of one or more of the perforations <NUM> can facilitate expansion of the flexible enclosure <NUM> out from the cover 380b.

As used herein, the terms "attached," "connected," "mated," and other such relational terms should be construed, unless otherwise noted, to include removable, moveable, fixed, adjustable, and/or releasable connections or attachments. The connections/attachments can include direct connections and/or connections having intermediate structure between the two components discussed.

The terms "approximately", "about", "generally" and "substantially" as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result. Any terms generally associated with circles, such as "radius" or "radial" or "diameter" or "circumference" or "circumferential" or any derivatives or similar types of terms are intended to be used to designate any corresponding structure in any type of geometry, not just circular structures. For example, "radial" as applied to another geometric structure should be understood to refer to a direction or distance between a location corresponding to a general geometric center of such structure to a perimeter of such structure; "diameter" as applied to another geometric structure should be understood to refer to a cross sectional width of such structure; and "circumference" as applied to another geometric structure should be understood to refer to a perimeter region. Nothing in this specification or drawings should be interpreted to limit these terms to only circles or circular structures.

Claim 1:
A pressure-regulating vial adaptor (<NUM>) comprising:
a connector interface;
a piercing member (<NUM>) supported by a body portion (<NUM>), wherein the piercing member is in communication with the connector interface;
a regulator channel (<NUM>) extending between the piercing member and a proximal regulator aperture; and
a regulator assembly (<NUM>') comprising:
a regulator base (<NUM>) comprising an annular wall, the regulator base having a coupling protrusion configured to couple to a regulator lumen, the regulator lumen being in communication with the piercing member;
a regulator nest (<NUM>) being configured to couple with the regulator base;
a flexible enclosure being positioned within a storage chamber within the regulator nest, the flexible enclosure being configured to transition between a stored configuration and an expanded configuration; and
a cover (380b) being connected to the annular wall of the regulator base, the cover comprising an aperture (<NUM>) and an annular side portion (<NUM>) sized and shaped to fit around a radially-outward portion of the regulator base, characterized in that the annular side portion of the cover is configured to cover an outer surface of the annular wall of the regulator base, the cover being further configured to inhibit expansion of the flexible enclosure and permit the flexible enclosure to at least partially extend through the aperture as the flexible enclosure transitions from the stored configuration towards the expanded configuration;
wherein the flexible enclosure is positioned within the storage chamber when the flexible enclosure is in the stored configuration and at least a portion of the flexible enclosure is positioned outside of the storage chamber when the flexible enclosure is in the expanded configuration.