BACKGROUND

The present disclosure pertains generally to devices (e.g., containers such as syringes or vials), systems and methods of filling devices with a fluid.

Existing syringes include a barrel, a plunger positioned within the barrel, and a plunger rod attached to the plunger. The plunger rod is actuatable to move the plunger between a forward end and a rearward end of the barrel. To fill such syringes, fluid may be introduced inside the barrel of the syringe through an opening in the forward end of the barrel or through the rearward end. These filling methods, however, have drawbacks.

When filling a syringe through the opening in the forward end, the plunger is moved in a rearward direction (e.g., away from the forward end) by the plunger rod. This movement of the plunger forms a region inside the barrel having a lower pressure than that outside of the barrel so that fluid is drawn inside the barrel through the forward opening. In such instances, the rearward end of the barrel is open and exposed to the environment, including the interior surface of the barrel on the rearward side of the plunger, so the plunger rod can extend from the plunger to a location outside of the barrel and be accessible to an operator. While the plunger may provide a sterile seal between the fluid inside the barrel and the environment, portions of the interior surface initially rearward of the plunger may become contaminated. Accordingly, when the plunger is moved rearward those portions may become exposed to the fluid and, thereby, introduce a contaminate to the fluid.

When filling a syringe from the rearward end, existing syringes may either have the plunger removed or punctured so that fluid may be positioned between the plunger and the forward end of the syringe barrel. Such steps, however, may similarly introduce contaminants into the chamber and the fluid through and/or around the plunger. Accordingly, there is a desire for improved arrangements and methods in this field that are capable of reducing the chance of the contents of device becoming contaminated during a fill procedure. SUMMARY

The present disclosure pertains generally to devices (e.g., containers such as syringes or vials), systems and methods of filling devices with a fluid. In certain aspects, rigid-wall containers having a movable piston and a flexible fill tube having a lumen in fluid communication with an adjustable-volume chamber are envisioned.

Disclosed devices can comprise: a barrel, a piston, an end cap, and a flexible fill tube; wherein the barrel defines a chamber having a first end and a second end; wherein the piston is positioned within the chamber and is slidable along a length of the chamber from a first position to a second position, the piston having a first side facing the first end of the chamber and a second side facing the second end of the chamber; wherein the end cap closes the second end of the chamber and has a first side facing the first end of the chamber and a second side opposing the first side; and wherein the flexible fill tube extends from the piston to the end cap and has a lumen in fluid communication with the first side of the piston through an opening in the piston and in communication with the second side of the end cap through a fill opening defined by the end cap.

A first end of the flexible fill tube can be fixedly attached in the piston and/or a second end of the flexible fill tube can be fixedly attached in the end cap. In some instances, the flexible fill tube is self-coiling tubing.

The barrel can be a syringe barrel and the piston can be a syringe plunger.

Alternatively, the barrel can be a vial barrel.

The second side of the piston can include a threaded portion for threadably coupling to a rod. Kits containing a device having a piston with a threaded portion can include the rod.

The end cap can define a vent opening arranged to vent gas into and/or from a portion of the chamber positioned between the piston and the end cap. In some instances, the vent opening includes a microbial filter. The end cap can include a port, such as a luer connector, in communication with the fill opening defined by the end cap. The port can be a needleless port and/or can include a valve. The end cap can be fixedly attached to the barrel or, alternatively, can be slidably (rotational and/or translational) attached to the barrel. For example, the end cap can be threadably attached to the barrel.

In any disclosed arrangement, the first end of the chamber can be closed with a needle penetrable septum, a valve, and/or a removable cap. Similarly, any of the disclosed devices can be sealed in a sterile environment within a package and/or a kit. In many instances, the flexible fill tube is positioned entirely within the rigid-wall container and extends between the movable piston and an end cap of the container when the piston is positioned within the container and the end cap is positioned to close an end of a chamber of the container.

Methods of filling devices are also provided. For example, methods of filling a device can comprise: passing a first fluid from the fill opening in the end cap, through the flexible fill tube, and into a portion of the chamber on the first side of the piston. In many

arrangements, passing the first fluid moves the piston from the first position to the second position and moves gas from a portion of the chamber between the piston and the end cap through a vent opening of the end cap. Additionally or alternatively, the methods can include removing the end cap after passing the first fluid through the flexible fill tube and into a portion of the chamber on the first side of the piston; and closing the lumen of the flexible fill tube. The closing can comprise heat sealing walls of the flexible fill tube together. In some instances, the method comprises returning the end cap to a position closing the second end of the chamber after closing the flexible fill tube.

Advantageously, devices, systems and methods of the present disclosure can enable the partial and/or complete filling of a chamber of an adjustable-volume container while maintaining sterility of the interior of the chamber. Specifically, the present disclosure provides arrangements wherein a movable wall of the adjustable-volume container is contained and movable within a sterile field. For example, the present disclosure provides arrangements wherein the adjustable- volume container has a piston positioned within the container and slidable along an interior wall of the container from a first position in a sterile region to a second position in a sterile region.

Further forms, objects, features, aspects, benefits, advantages, and embodiments of the present invention will become apparent from a detailed description and drawings provided herewith. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of an exemplary device of the present disclosure.

FIG. 2 illustrates the piston of the device of FIG. 1 in a second position.

FIG. 3 illustrates the device of FIG. 1 with the end cap removed and the lumen of the flexible fill tube closed.

FIG. 4 illustrates the device of FIG. 3 with the end cap returned to close the end of the barrel chamber.

FIG. 5 illustrates an actuating rod usable to move a piston.

FIG. 6 illustrates an actuating rod attached to a piston

FIG. 7 illustrates expelling fluid from the device of FIG. 6.

FIGs. 8 and 9 illustrate a device having a needle penetrable septum closing the first end of the barrel chamber.

FIG. 10 illustrates a cross-sectional view of an adaptor attachable to the first end of the device and useful to withdraw fluid from the device.

FIGs. 11 and 12 illustrate various connectors for the adaptor of FIG. 10.

FIG. 13 illustrates an exemplary device before being filled from its fluid-dispensing end.

FIG. 14 illustrates an exemplary device after being filled from its fluid-dispensing end.

FIG. 15 illustrates another exemplary device fillable from its fluid-dispensing end.

DESCRIPTION OF THE SELECTED EMBODIMENTS

For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Any alterations and further modifications in the described embodiments, and any further applications of the principles of the invention as described herein are contemplated as would normally occur to one skilled in the art to which the invention relates. One embodiment of the invention is shown in great detail, although it will be apparent to those skilled in the relevant art that some features that are not relevant to the present invention may not be shown for the sake of clarity.

An exemplary device 100 (e.g., a container such as syringe or vial) of the present disclosure comprises a barrel 102, a piston 104, an end cap 106 and a flexible fill tube 108. The barrel has an inside surface 112 defining a chamber 114 having a first end 116 and a second end 118, and the piston is slidably positioned within the chamber. The barrel can have openings at the first and/or second ends. The barrel can define a cylindrical chamber.

The barrel can be formed of a variety materials including, but not limited to, glass or cyclic olefin copolymer (COC). In many instances, the barrel has a rigid wall having a higher modulus of elasticity than the piston and/or the flexible fill tube. For example, the barrel can have a wall having an elastic modulus that is at least 50%, at least 100%, and/or at least 200% that of the piston and/or flexible fill tube.

The piston has a side edge 122 in contact with and slidable along the inside surface of the barrel. The piston has a first side 124 facing the first end of the chamber and a second side 126 facing the second end of the chamber. The first side of the piston defines an opening 130. The opening 130 allows fluid communication between a lumen 132 of the fill tube 108 and the first side 124 of the piston. Additionally, in some instances, the second side of the piston includes a rod coupling portion 134 for coupling an actuating rod with the piston. The rod coupling portion can include threads 136 for threadably coupling the piston with an actuating rod.

The end cap is arranged to close the second end of the chamber. The end cap has a first side 140 and a second side 142 and a side edge 144. In many instances, when the end cap is positioned to close the second end of the chamber, the first side of the end cap faces the chamber (e.g., the second end of the chamber) and the second side faces away from the chamber (e.g., opposing the first side). The end cap can be arranged to have a portion slidably received within the barrel of the device. For example, the first side of the end cap can be slidably receivable within the barrel with the side edge of the end cap in sliding contact with the inner surface of the barrel.

The end cap can define a vent opening 148. The vent opening can be arranged to vent fluid (e.g., gas) into and/or out of a chamber portion through the end cap. For example, the vent opening can allow a gas to move from the chamber portion on the first side of the end cap to an area on second side of the end cap and/or vice versa. In such an arrangement, the vent opening can extend from the first side to the second side of the end cap.

The vent opening can include a filter material 150, such as a microbial filter. The filter material is arranged to filter fluid (e.g., gas) as it passes through the vent opening. For example, the filter material can be arranged to filter air as is passes through the end cap and into the chamber portion positioned between the end cap and the piston.

The end cap can have a port 162, and the port can be in fluid communication with the lumen of the flexible fill tube. For example, the port can be associated with a fluid channel extending through the end cap so as to allow passage of fluid through the end cap and into the lumen of the flexible fill tube. In many instances, the port is positioned on the second side of the end cap. The port can be a needleless port.

The port of the end cap can be arranged to allow attachment of a second device, such as a syringe, so that contents of the second device are in fluid communication with the lumen of the flexible fill tube and can pass through the end cap. For example, in one exemplary use, fluid is passed from a syringe connected to the port through the end cap, through the flexible fill tube, and through the piston into a portion of the chamber positioned on the first side of the piston. The port can include a luer connector, such as one suitable for connecting to a syringe and/or medical tubing.

The flexible fill tube 108 extends from the piston to the end cap. The flexible fill tube has a wall portion 152 defining the lumen 132. As explained above, the lumen can provide fluid communication from the second side of the end cap to the first side of the piston. In some instances, the flexible fill tube has a first end 156 fixedly attached to the piston and a second end 158 fixedly attached to the end cap.

The flexible fill tube can have a preformed configuration that the tubing returns to when external force is removed from the tubing. For example, such tubing can be

configurable from an uncoiled, first condition into a coiled, second configuration when external force on the tubing is removed. The tubing, therefore, can be self-coiling tubing. In the first condition, the flexible fill tube can extend substantially linearly from the first end of the tubing to the second end of the tubing. In the second condition, the flexible fill tube can form a coil (e.g., a helical coil) wherein portions of the flexible fill tube lie alongside one another along a length of the flexible fill tube. In some instances, the flexible fill tube is arranged to transition from a coiled arranged to an uncoiled arrangement when the ends of the flexible fill tube are forced away from one another under a force of 5 Newtons or less.

The flexible fill tube can comprise any of a variety of materials, including

fluoroelastomers and thermoplastics, just to name a few examples. The flexible fill tube can comprise, urethane, flexible polyvinyl chloride (PVC), polyethylene, ethyl vinyl acetate (EVA), silicone, neoprene, rubber, and/or polytetrafluoroethylene (PTFE). The flexible fill tube can, in some instances, be free of latex, plasticizer, phthalate, and/or DEHP.

In any embodiment, device 100 can include a port 166 at the first end 116 of the chamber 114 and arranged for the withdrawal of fluid from the chamber 114. In some instances, the port 166 can be closed with an end cap 170. The port can have a needle penetrable septum. Alternatively or additionally, the port 166 can include a valve, a luer connector, such as one suitable for connecting port 166 to a syringe and/or medical tubing, and/or a needle.

The devices described herein can be provided in sterilely sealed kits and packages. For example, the devices disclosed herein can be sterilized and sealed in a sterile package or sealed within a package and subsequently sterilized. Such sterilization can include sterilization by physical, chemical, and/or irradiation means (e.g., high temperature sterilization, ethylene oxide (ETO) sterilization, chlorine dioxide (CD) gas sterilization, UV light irradiation, x-ray irradiation, gamma ray irradiation, and/or electron bean irradiation). In some instances, devices disclosed herein can be provided in kits having other attachable devices useful in the filling and/or withdrawal of fluid in the device(s). For example, such kits can include one or more devices disclosed herein as well as a system (e.g., manifold and syringes) for filling the one or more devices. The kits can include fluid (e.g., biologies) with which to fill the one or more devices.

A mode of operation of the device 100 will now be described with regard to FIGS. 1- 4. In an initial configuration (as shown in FIG. 1), the first end 116 of the chamber 114 is closed, such as with a cap and/or a needle penetrable septum, and the piston is positioned within the chamber proximate the first end. The second end of the chamber 114 is closed with the end cap, defining a chamber portion extending between the piston and the end cap. The chamber portion extending between the piston and the end cap is a sterile chamber portion. For example, the chamber portion can be, or have been, sterilized by physical, chemical, and/or irradiation means (e.g., high temperature sterilization, ethylene oxide (ETO) sterilization, chlorine dioxide (CD) gas sterilization, UV light irradiation, x-ray irradiation, gamma ray irradiation, and/or electron bean irradiation).

To partially or completely fill the device (e.g., with a pharmaceutical), fluid is passed through the first opening 146 in the end cap, through the flexible fill tube, and through the piston opening so as to be positioned into the chamber portion in fluid communication with the first side 124 of the piston. As the fluid is passed into the chamber portion on the first side 124 of the piston, the fluid pressure on the first side 124 of the piston increases to an amount sufficient to overcome the frictional force between the side edge 122 of the piston and the inside surface 112 of the barrel such that the piston moves from a first position (such as that illustrated in FIG. 1) to a second position (such as that illustrated in FIG. 2). As the piston moves toward the end cap, fluid (e.g., gas) in the chamber portion between the piston and the end cap escapes through the vent in the end cap.

Once a desired quantity of fluid is positioned in the chamber on the first side 124 of the piston, the port in the end cap can be closed and/or the end cap can be removed from the second end of the chamber and the lumen of the flexible fluid fill tube can be closed. The lumen flexible fluid fill tube can be closed by bringing a first internal surface 180 and a second internal surface 182 of the flexible fluid fill tube into contact with one another at a location 184 and fusing the two together, such as by heat sealing/welding (as shown in FIG. 3). The end cap can then be returned to the second end of the chamber (as shown in FIG. 4) or it can be severed from the flexible fill tube and discarded. The container (e.g., vial and/or syringe) may then be stored. For example, the container may be positioned within a freezer including, but not limited, a cryogenic freezer.

Advantageously, as the end cap closes the second end of the chamber so as to define a sterile chamber portion between the piston and the end cap, the piston travels into a sterile portion of the device (e.g., along sterile portions of the inside surface 112 of the barrel 102) when the device is being partially and/or completely filled. In contrast, arrangements lacking an end cap or other similar structure can have portions of the inside surface into which the piston can move be unsterile. As a result, such unsterile portions can potentially introduce contaminates into the fluid positioned within the chamber on the first side of the piston as the piston moves along and inner surface of the barrel. The present invention can advantageously allow for the expansion and/or contraction of the fluid retained in the barrel without compromising the sterile integrity of the device. For example, when positioned within a cryogenic freezer after being partially and/or completely filled, the fluid in the container may expand upon freezing. The piston of the device allows for movement to accommodate for the expansion and/or contraction of fluid, without the pressure inside the barrel exceeding a threshold that can compromise the structure of the device (e.g., fracture a portion of the device and/or eject the end cap, septum and/or valve closing the first end of the barrel).

Fluid can be dispensed from the first end of the chamber. For example, the piston can be forced towards the first end of the chamber so that fluid is dispensed from the device, such as through the port 166 at the first end of the chamber. FIG. 5 illustrates an exemplary rod that can be coupled to the piston and used to push the piston to deliver fluid from the device, as shown in FIGs. 6 and 7. An end cap (e.g., end cap 170) closing the opening (e.g., port 166) at the first end of the chamber may be removed prior to fluid being dispensed from the opening.

As shown in figure 9 and mentioned above, the container can have a needle- penetrable septum 300 at the first end of the chamber. The needle-penetrable septum can be useful to withdraw fluid from the chamber portion on the first side of the piston.

The container can be arranged to cooperate with one or more adaptors to remove fluid from the container. For example, an adaptor 400 may have a recess 402 arranged to receive at least a portion of the container. In the recess can be a needle 404 for penetrating a wall (e.g., a needle -penetrable septum) of a container and, thereafter, communicate with the contents of the container. The adaptor can include a locking portion (e.g., groove 406) arranged to receive a locking portion 302 of the container such that when the two are mated the adaptor is locked to the container with the needle penetrating a wall of the container. In fluid communication with the needle of the adaptor is a connector, such as a male luer 408 and/or a female 410. Alternatively, the adaptor may have tubing and/or a needle 412 communicating with the needle inside the recess.

Variations of the above described devices and methods are envisioned. For example, as illustrated in figures 13 and 14, a device may be arranged for filling and/or dispensing from the first end 116 of the chamber 114. In such an arrangement the flexible fill tube and openings in the piston and the end cap communicating with the lumen of the flexible fill tube may be omitted. Notably, however, the end cap can still have a filter that allows for the venting of air into and/or out of the portion of the chamber on the second side of the piston. Accordingly, the area of the chamber the piston travels into during filling (or expansion while freezing) maintains its sterility even after the device is removed from sterile medical packaging.

In the arrangements wherein the device is filled from the first end, it is contemplated that the port 166 may be sealed with a valve, a cap, and/or by sealing the tubing used to fill the device. For example, a valve may be actuated and/or a luer cap may be positioned to close port 166. The luer cap may comprise a flexible material (e.g., silicone) to allow for expansion of the contents of the device during freezing. Regarding tubing, it may be sealed (e.g., welded) closed (as shown in figure 14) and remain in-place until the contents of the device are to be dispensed. Then, when an operator desires to withdraw fluid from the device, the operator may either sever and/or remove the tubing to achieve access to the fluid.

Figure 15 illustrates another variation of the device wherein the device includes a flexible membrane 190 (e.g., a plastic film and/or a bag) serving as a barrier between the inside surface 112 of the barrel and air positioned on the second side of the piston 104. The flexible membrane is preferably attached to the barrel at the second end 118.

Advantageously, the flexible membrane may gather during filling and/or extend during expulsion of fluid on the first side of the piston. As will be appreciated, the flexible membrane may be in addition to and/or replace the end cap and filter. Accordingly, the flexible membrane can maintain sterility of the inside surface of the chamber on the second side of the piston when the device is absent an end cap.

While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes, equivalents, and modifications that come within the spirit of the inventions defined by following claims are desired to be protected. All publications, patents, and patent applications cited in this specification are herein incorporated by reference as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated by reference and set forth in its entirety herein.

The language used in the claims and the written description is to only have its plain and ordinary meaning, except for terms explicitly defined below. Such plain and ordinary meaning is defined here as inclusive of all consistent dictionary definitions from the most recently published (on the filing date of this document) general purpose Merriam- Webster dictionary.

As used in the claims and the specification, the following terms have the following defined meanings:

The term“container” as used herein has the meaning an object that can be used to hold or transport a liquid. The term includes, but is not limited to, syringes, vials,

The terms“fill” and“filling” as used herein include complete fill/filling and partial fill/filling of a container.

The term“syringe” as used herein has the ordinary and customary meaning as understood by those in the medical field. The term includes a device having a piston useful to inject fluids into and/or withdraw them from a patient’s body.

The term“vial” as used herein has the meaning, a small container arranged to hold liquid and allow for subsequent withdrawal of the liquid. This includes, but is not limited to, containers having a volume of less than 10 mL or less than 6 mL. The term also includes rigid-wall containers, such as a container with a glass or rigid-plastic wall. The vials described herein include vials for cryopreservation. The term includes the vials described and/or illustrated in U.S. Patent No. 7,939,316 published on May 10, 2011; U.S. Patent No. 8,222,027 published on July 17, 2012; PCT Publication No. WO 2013/023075 published on April 4, 2013; U.S. Patent No. 8,936,905 published on January 20, 2015; U.S. Publication No. 2015/0140650 published on May 21, 2015; U.S. Patent No. 9,565,854 published on

February 14, 2017; and U.S. Publication No. 2017/0099832 published on April 13, 2017. The term includes vials having a tubular body with a needle-penetrable septum so as to allow for aseptic withdrawal of fluid from inside the tubular body. Certain vials may include one or more tubes extending from the tubular body, the first and second tubes communicating with the interior of the tubular body. The first and second tubes may be heat sealable. In some instances, the first tube can have a Luer fitting. Additionally or alternatively, the second tube can include a sterile filter, such as an anti-microbial filter. The filter can have a nominal micron rating between about 10 and 0.1 microns. In some instances, the filter has a nominal micron rating between 5 and 0.1 microns and/or between about 3 and 0.2 microns. The filter can have a nominal micron rating of approximately 0.1 microns. The first and second tubes can extend from an end of the vial opposite of a needle -penetrable septum. The following numbered clauses set out specific embodiments that may be useful in understanding the present invention:

1. A device, comprising:

a barrel, a piston, an end cap, and a flexible fill tube;

wherein the barrel defines a chamber having a first end and a second end;

wherein the piston is positioned within the chamber and is slidable along a length of the chamber from a first position to a second position, the piston having a first side facing the first end of the chamber and a second side facing the second end of the chamber;

wherein the end cap closes the second end of the chamber and has a first side facing the first end of the chamber and a second side opposing the first side; and

wherein the flexible fill tube extends from the piston to the end cap and has a lumen in fluid communication with the first side of the piston through an opening in the piston and in communication with the second side of the end cap through a fill opening defined by the end cap.

2. The device of clause 1, wherein a first end of the flexible fill tube is fixedly attached in the piston. 3. The device of any preceding clause, wherein a second end of the flexible fill tube is fixedly attached in the end cap.

4. The device of any preceding clause, wherein the barrel is a syringe barrel and the piston is a syringe plunger.

5. The device of any preceding clause, wherein the second side of the piston includes a threaded portion for threadably coupling to a rod.

6. The device of any one of clauses 1-3, wherein the barrel is a vial barrel.

7. The device of any preceding clause, wherein the end cap defines a vent opening arranged to vent gas from a portion of the chamber between the piston and the end cap. IB

8. The device of clause 7, wherein the vent opening includes a microbial filter.

9. The device of any preceding clause, wherein the end cap has a luer connector in communication with the fill opening defined by the end cap.

10. The device of any preceding clause, wherein the first end of the chamber is closed with a needle penetrable septum.

11. The device of any preceding clause, wherein the first end of the chamber is closed with a removable cap.

12. The device of any preceding clause, wherein the device is sealed in a sterile environment within a package. 13. The device of any preceding clause, wherein the flexible fill tube is self-coiling tubing.

14. A method of filling the device of any preceding clause, comprising:

passing a first fluid from the fill opening in the end cap, through the flexible fill tube, and into a portion of the chamber on the first side of the piston.

15. The method of clause 14, wherein:

passing a first fluid moves the piston from the first position to the second position and moves gas from a portion of the chamber between the piston and the end cap through a vent opening of the end cap.

16. The method of clause 14 or clause 15, comprising:

removing the end cap after passing the first fluid through the flexible fill tube and into a portion of the chamber on the first side of the piston; and

closing the lumen of the flexible fill tube.

17. The method of clause 16, wherein the closing comprises heat sealing walls of the flexible fill tube together. 18. The method of clause 16 or clause 17, comprising:

returning the end cap to a position closing the second end of the chamber after the closing.