Apparatus and method for sterile transfer of fluid from a fluid container - Patents.com

Abstract

A sterile closure assembly for a fluid container including a cap connectable to an opening of the fluid container and a fluid dispenser connectable to an exterior surface of a housing of the cap. The fluid dispenser includes a body, a fluid line disposed within the body, a shell housing disposed about the body, and an insert connectable to a second end of the body. The body includes an opening near the second end that is connected to the fluid line and that is configured to be in fluid communication with the fluid container when the fluid dispenser is connected to the cap. The fluid dispenser is configured such that a downward force toward the fluid container causes the insert to engage a support in the cavity and the insert to disconnect from the body of the fluid dispenser to seal the fluid container.

Description

[Technical field]

[0001] Priority This disclosure claims priority to U.S. Provisional Application No. 63 / 303,016, filed January 25, 2022, which is incorporated by reference herein.

[0002] The present disclosure relates generally to a system for the sterile transfer of fluid from a fluid container. More particularly, the present disclosure relates to a sterile closure assembly, including a cap and a fluid dispensing assembly, methods, and components for the sterile transfer of fluid from a fluid container. [Background technology]

[0003] Chemical and / or biological processes may utilize or produce process materials that are stored in storage vessels, such as bioprocessing bags, bottles, etc., with rigid connection systems, containing pharmaceutical or biological fluids, acids, solvents, bases, photoresists, dopants, inorganic solutions, organic solutions, etc. The process materials may need to be frozen or otherwise kept at low temperature in the storage vessels. When using such fluids, the storage vessels need to adequately contain the chemicals during storage, transportation, and ultimately during the manufacturing process itself. However, currently, methods and fluid transfer assemblies for transferring fluids to and from storage vessels with rigid connection systems are unable to ensure sterility of the system. Summary of the Invention

[0004] The present disclosure relates generally to a system for the sterile transfer of fluid from a fluid container. More particularly, the present disclosure relates to a sterile closure assembly, including a cap and a fluid dispensing assembly, methods, and components for the sterile transfer of fluid from a fluid container.

[0005] In one embodiment, a sterile closure assembly for a fluid container is provided. The sterile closure assembly includes a cap connectable to an opening of the fluid container, the cap having a housing, a cavity in the housing with a support, and a first set of seals, and a fluid dispenser connectable to an exterior surface of the housing of the cap. The fluid dispenser includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an insert connectable to the second end of the body. The body includes an opening near the second end that is connected to the fluid line and that is configured to be in fluid communication with the fluid container when the fluid dispenser is connected to the cap. The fluid dispenser is further configured such that a downward force toward the fluid container causes the insert to engage the support of the cavity and the insert to disconnect from the body of the fluid dispenser to seal the fluid container.

[0006] In another embodiment of the invention, a sterile closure assembly is provided that includes a cap connectable to an opening of a fluid container, the cap including a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals. The port includes a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port, and a fluid dispenser connectable to an exterior surface of the port shell. The fluid dispenser includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an engagement piece engageable with the insert. The engagement piece of the fluid dispenser is engageable with the insert of the port by rotational engagement such that the fluid line can be directed downwardly toward the fluid container together with the insert so that the fluid communication channel with the fluid container is opened.

[0007] In one embodiment, a method for sterile transfer of fluid into or out of a fluid container is provided. The method includes connecting a cap to an opening of the fluid container, the cap including a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals. The port includes a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port. The method further includes transferring fluid into the fluid container by aseptically connecting and disconnecting a fluid dispenser to an exterior surface of the port shell. The fluid dispenser includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an engagement piece engageable with the insert. When the engagement piece of the fluid dispenser is engaged with the insert of the port through rotational engagement, the fluid line can be directed downwardly together with the insert towards the fluid container such that a fluid communication channel with the fluid container is open.

[0008] In yet another embodiment, a fluid dispenser connectable to an exterior surface of a cap of a fluid container is provided. The fluid dispenser includes a body having a first end and a second end, the body including a fluid line disposed between the first end and the second end, and a shell housing disposed about the body. The fluid line at the second end of the body is configured to be connectable with an insert disposed in the cap by rotating the body, and the shell housing includes a compressible bellows to allow for sterile insertion of the fluid line into the fluid container. [Brief description of the drawings]

[0009] [Figure 1] 1 is a schematic diagram of a sterile closure assembly according to one embodiment. [Figure 2A] 2A-2B are exploded and perspective views of the cap and fluid dispenser according to FIG. [Figure 2B] 2A-2B are exploded and perspective views of the cap and fluid dispenser according to FIG. [Figure 3A] 3A, 3B and 3C are cross-sectional views of the sterile closure assembly of FIG. 1 illustrating the connection of a fluid dispenser and a cap and the transfer of fluid therein, according to one embodiment. [Figure 3B] 3A, 3B and 3C are cross-sectional views of the sterile closure assembly of FIG. 1 illustrating the connection of a fluid dispenser and a cap and the transfer of fluid therein, according to one embodiment. [Figure 3C] 3A, 3B and 3C are cross-sectional views of the sterile closure assembly of FIG. 1 illustrating the connection of a fluid dispenser and a cap and the transfer of fluid therein, according to one embodiment. [Figure 3D] 3D-3E are cross-sectional views of the sterile closure assembly of FIG. 1 illustrating disconnection of the fluid dispenser and the cap according to one embodiment. [Figure 3E] 3D-3E are cross-sectional views of the sterile closure assembly of FIG. 1 illustrating disconnection of the fluid dispenser and the cap according to one embodiment. [Figure 4A] 4A-4B are cross-sectional views of a sterile closure assembly, according to one embodiment, showing the connection of a fluid dispenser and an insert. [Figure 4B] 4A-4B are cross-sectional views of a sterile closure assembly, according to one embodiment, showing the connection of a fluid dispenser and an insert. [Figure 5A] 5A-5B are perspective and cross-sectional views of another embodiment of a sterile closure assembly. [Figure 5B] 5A-5B are perspective and cross-sectional views of another embodiment of a sterile closure assembly. [Figure 6A] 6A, 6B and 6C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B, according to one embodiment. [Figure 6B] 6A, 6B and 6C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B, according to one embodiment. [Figure 6C]6A, 6B and 6C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B, according to one embodiment. [Figure 7A] 7A, 7B and 7C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B according to another embodiment. [Figure 7B] 7A, 7B and 7C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B according to another embodiment. [Figure 7C] 7A, 7B and 7C are perspective, exploded and cross-sectional views of a cap of the sterile closure assembly of FIGS. 5A-5B according to another embodiment. [Figure 8A] 8A and 8B are perspective and cross-sectional views of the sterile closure assembly of FIGS. 5A-5B, illustrating the connection of a fluid dispenser and a cap, according to one embodiment. [Figure 8B] 8A and 8B are perspective and cross-sectional views of the sterile closure assembly of FIGS. 5A-5B, illustrating the connection of a fluid dispenser and a cap, according to one embodiment. [Figure 8C] 8C and 8D are perspective views of the sterile closure assembly of FIGS. 5A-5B with a fluid container according to one embodiment. [Figure 8D] 8C and 8D are perspective views of the sterile closure assembly of FIGS. 5A-5B with a fluid container according to one embodiment. [Figure 9A] 9A and 9B are cross-sectional views of a secondary body and a second port of a sterile closure assembly according to one embodiment. [Figure 9B] 9A and 9B are cross-sectional views of a secondary body and a second port of a sterile closure assembly according to one embodiment. [Figure 10A] 10A and 10B are cross-sectional views of a secondary body and a second port of a sterile closure assembly according to another embodiment. [Figure 10B] 10A and 10B are cross-sectional views of a secondary body and a second port of a sterile closure assembly according to another embodiment. [Figure 11A]11A and 11B are perspective views of a secondary body and a second port of a sterile closure assembly according to the embodiment of FIGS. 10A-10B. [Figure 11B] 11A and 11B are perspective views of a secondary body and a second port of a sterile closure assembly according to the embodiment of FIGS. 10A-10B. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Like numbers refer to like features.

[0011] The present disclosure generally relates to a sterile closure assembly for the aseptic transfer of fluid from a fluid container. More particularly, the present disclosure relates to a sterile closure assembly including a cap and a fluid dispensing assembly used to couple to and aseptically transfer, e.g., fill and remove, fluid from a storage container to avoid contamination. As used herein, the term aseptic refers at least to forming an unbroken barrier or fluid pathway between the fluid dispensing assembly and the fluid container to keep the fluid substantially free of contaminants from the external environment for the purpose of maintaining the sterility of the internal contents and / or components. Fluids associated with chemical and / or biological processes are discussed below, but it is understood that such discussion is not intended to limit the scope of the invention, but is provided as an embodiment of the invention. Fluids include, but are not limited to, substances that flow or deform when subjected to shear stress. Fluids can include, for example, liquids.

[0012] For example, in the bioprocessing market, customers freeze, ship, and thaw their drug products in various fluid storage containers such as bottles, bags, pails, drums, etc. Although customers can use various sterile connectors to aseptically transfer fluids to bag assemblies, the use of bottles, pails, drums, or larger bag assemblies is not as widely used because the transfer of fluids to and from those bottles, pails, drums, or larger bag assemblies cannot be done using a simple sterile connection assembly, e.g., because the fluid transfer assembly is connected to the top of the bottle, pail, drum, or larger bag assembly, the transfer of fluids is not in a closed system and requires additional equipment or mechanisms to maintain the sterility of the fluid. For example, a customer may use a bottle with a cap at its top opening that has a tubing connection port or a polymer stopper that covers the top opening of the bottle. The cap can be used to aseptically fill the bottle, and the polymer stopper can be used to close the bottle, but in either case, the customer must either remove the cap and replace it with a sturdy cap for the process steps of freezing, shipping, and thawing, or remove the polymer stopper to fill and / or remove the fluid, e.g., drug product. However, replacing the bottle cap and / or polymer stopper opens the system and exposes the fluid in the bottle to the outside environment, which can lead to possible contamination of the fluid. To limit and / or reduce the amount of contaminants that can enter the bottle during replacement of the bottle cap and / or polymer stopper, a hood can be used to attempt to maintain the sterility of the system. To simplify the filling and removal of fluid from the bottle, e.g., without requiring the use of a hood or additional equipment to maintain the sterility of the system, and to reduce the possibility of contaminating the fluid in the bottle, a system is needed for aseptically transferring fluid from a fluid storage container, such as a bottle, pail, drum, etc.

[0013] Embodiments of the present disclosure are directed to a sterile closure assembly including a cap and a fluid dispenser that allows for the sterile transfer of fluid from a fluid container, such as a bottle or other fluid container having a rigid opening, such as a pail, bucket, or larger bag assembly having a rigid opening that is matable with the cap. It is understood that a rigid opening, as used herein, refers to at least an opening formed in the fluid container that is fabricated from a relatively rigid material, such as one or more polymers. For example, the fluid enclosure may be fabricated from polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polycyclohexylene dimethylene terephthalate (PCTA), polycyclohexylene dimethylene terephthalate glycol (PCTG), polycarbonate (PC), polypropylene (PP), poltamide (PA), polyethersulfone (PES), polyphenylsulfone (PPSU), polymethyl methacrylate (PMMA), high impact polystyrene (HIPS), polyethylene naphthalate (PEN), polyether ether ketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, fluoropolymers, and the like, and copolymers containing these materials.

[0014] The sterile cap and fluid dispenser may include a multi-purpose sterile cap that allows a user to aseptically connect and disconnect to a rigid opening of a body storage container, such as a bottle or a rigid opening of a bag assembly, before and after a freeze / thaw process step. The sterile closure assembly may allow a user to fill the bottle before freezing and drain the bottle after thawing without having to replace the cap and / or polymer stopper during the filling and draining process, avoiding the destruction of the sterile barrier and / or fluid pathway between the fluid dispenser and the fluid storage container. The sterile cap and fluid dispenser allow the bottle to be used as a closed system, preventing contamination of the fluid by, for example, being open to the outside environment, and maintaining the sterility of the fluid in a fluid processing system, particularly for bioprocessing fluid processing. It will be appreciated that due at least in part to this design and construction of the sterile closure assembly, the fluid reservoir and sterile closure assembly can be used in freeze / thaw process steps in applications down to -85°C where there are currently no existing sterile cap designs that are rated as suitable for use under such conditions, and particularly for use with such top-delivery and removal devices. Although the description of the fluid reservoir and sterile closure assembly has been discussed with respect to temperatures as low as -85°C, it will be appreciated that the fluid reservoir and sterile closure assembly can also be used at cryogenic temperatures, for example, below -190°C, and even more preferably below -196°C.

[0015] 1 is a schematic diagram of a sterile closure assembly 10 for a fluid container 1, according to one embodiment. The sterile closure assembly 10 can include a cap 12 connectable to a top opening of the fluid container 1, and a fluid dispenser 14, where the cap 12 and the fluid dispenser 14 are configured to be joined together to form a sealed fluid connection. The fluid dispenser 14 includes a fluid passageway extending from the opening through the fluid dispenser 14. The cap 12 is configured to sterilely connect the fluid passageway of the fluid dispenser 14 to the fluid container 1 to provide sterile fluid communication when the fluid dispenser 14 is connected to the cap 12, as discussed further below.

[0016] In this manner, the sterile closure assembly 10 is configured to be sterilely connected and disconnected to a fluid container for sterile transfer of fluid to and from a fluid container usable at temperatures as low as -85°C. It is appreciated that the sterile closure assembly 10 may be used at other temperatures, such as 0°C, room temperature, etc., while maintaining the benefits of the present disclosure. Thus, a fluid container 1 having a sterile closure assembly 10 as discussed above is configured to be stored at freezing temperatures (e.g., temperatures below 0°C). In one embodiment, a fluid container 1 having a sterile closure assembly 10 may also be heated and returned to ambient temperatures without any substantial deformation. Substantial deformation may include, for example, visible cracking of the material, shrinkage or expansion relative to its original shape at ambient temperatures, which may interfere with or adversely affect the sealing of said connections. Low temperature elastic recovery testing may be performed according to ASTM D1329, ISO 2921, or any other suitable test method for determining suitable shrinkage characteristics of a material at temperatures that may be used. The brittleness test can be carried out according to ASTM D2137, ISO 28702, or any other suitable test method for determining the resistance to cracking of a material at the temperatures that may be used.

[0017] Fluid enclosure 1 may be used to contain fluids generally, for example, liquids suitable for use in manufacturing and / or biological processes, such as, but not limited to, semiconductor manufacturing, pharmaceutical manufacturing, or biological processing, etc. In this regard, it will be appreciated that fluid enclosure 1 may store liquid chemicals, including, but not limited to, liquid chemicals such as photoresists, acids, solvents, bases, dopants, inorganic solutions, organic solutions, pharmaceuticals, biological fluids, and the like.

[0018] In one embodiment, the fluid container 1 can be a plastic bottle and / or a bag-in-bottle or bag-in-can style container. In other embodiments, the fluid container 1 can be a bag assembly having a rigid connection structure, such as, for example, a boat fitment, a fitting, a plastic port, and the like, or a combination of the above. It will be appreciated that the container can be any type of container having a rigid opening 2 for attachment of a sterile closure assembly 10, as discussed below. Such a fluid container 1 (or a rigid connection structure) can be fabricated from a relatively rigid material, for example, one or more polymers. For example, the fluid enclosure 1 may be fabricated from polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polycyclohexylene dimethylene terephthalate (PCTA), polycyclohexylene dimethylene terephthalate glycol (PCTG), polycarbonate (PC), polypropylene (PP), poltamide (PA), polyethersulfone (PES), polyphenylsulfone (PPSU), polymethyl methacrylate (PMMA), high impact polystyrene (HIPS), polyethylene naphthalate (PEN), polyether ether ketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, and the like, and copolymers containing these materials.

[0019] The cap 12 is connectable to the rigid opening 2 of the fluid container 1 to secure the cap 12 to the fluid container 1. The cap 12 can be connected to the fluid container 1 by a press fit of the cap 12 into the rigid opening, or the cap 12 and the rigid opening 2 can include inter-engaging threads. It will be appreciated that the cap 12 can also be connected to the fluid container 1 in other manners, such as using mechanical fasteners, such as clamps, corresponding engagement mechanisms, or welding or joining techniques, such as thermal bonding, impulse welding, laser welding, ultrasonic welding, or similar fusion / melting welding techniques. In one embodiment, the cap 12 can be connected to the fluid container using a tamper-evident connection system. For example, the cap 12 with the tamper-evident connection system can include inwardly biasing retaining arms that, once pressed to a predetermined position on the rigid opening 2, engage corresponding protrusions around the rigid opening 2 of the fluid container 1, such that the cap 12 cannot be easily removed from the fluid container 1 without leaving visible signs of damage to the cap 12 and / or the fluid container 1. In another embodiment, the cap 12 with the tamper-evident connection system can include a protrusion on a lower portion of the threaded portion such that, once the cap 12 is threaded to a predetermined position, the cap 12 cannot be removed from the fluid container 12, for example, by reversing the rotation of the cap 12 on the rigid opening 2. In yet another embodiment, the tamper-evident connection system can include a ring on the cap 512 that separates from the cap 512 when the cap 512 is removed from the fluid container. In this case, the tamper-evident connection system can alert a customer or user of the fluid container 1 having the cap 12 if the fluid container 1 has been opened or attempted to be opened, and potentially contaminated and / or damaged.

[0020] 2A-2B show an embodiment of a sterile closure assembly 10 as described above. As seen in FIG. 2A, the sterile closure assembly 10 includes a cap 12 and a fluid dispenser 14. The fluid dispenser 14 includes a body 205 having a first end and a second end, a fluid line 210 disposed within the body between the first end and the second end, a shell housing 215 disposed around the body 205, a set of seals 220, and an insert 225 connectable to and / or releasable from the second end of the body 205. The insert 225 is connectable to and / or releasable from the second end of the body 205 by being press-fitted into the second end of the body, for example, the seal 220 disposed around the second end of the body 205. It will be appreciated that the insert 225 can also be connected to the body 205 using various structures that allow for connection and release of the insert 225. For example, in one embodiment, the second end of the body 205 may include an engagement portion or protrusion extending from the second end of the body 205 that engages with a corresponding recess provided in the insert 225. In this case, the engagement portion or protrusion on the second end of the body 205 may be inserted and rotated into the recess of the insert 225 for connection and release of the insert 225 from the body 205.

[0021] The fluid line 210 may include a tube connector toward the first end of the body 205 for connection to a fluid transfer system for transfer of fluid to, e.g., filling or removing, the fluid container 1. The tube connector may be selected from the group consisting of a hose barb, an overmolded connection, a threaded connection, a press-fit connection, a snap-fit ​​connection, or combinations thereof. It will be appreciated that the tube connector may also be formed contiguous with the fluid transfer system, for example, by molding or overmolding the fluid dispenser 14 together with the fluid transfer system.

[0022] The body 205 may also include an opening 206 toward the second end that is fluidly connected to the fluid line 210 and configured to be in fluid communication with the fluid container 1 when the fluid dispenser 14 is connected to the cap 12. The fluid dispenser 14 may also include an enlarged portion 230 that may be in fluid communication with the opening 206 provided through the body 205 such that when fluid is supplied or removed through the fluid line 210 of the fluid dispenser 14, fluid flows from the opening 206, through the enlarged portion 230, around the insert 225 and into the fluid container 1, or from the fluid container 1, around the insert 225, through the enlarged portion 230 and then through the opening 206. In one embodiment, the fluid dispenser 14 includes a first retention feature 235 for engaging an outer surface of a housing 240 of the cap 12, as discussed below.

[0023] 2B, the cap 12 includes a housing 240, a cavity 245 within the housing 240, a support 250 provided in the cavity 245, and a set of seals 255. The housing 240 of the cap 12 includes a second retention feature 260 having a shape complementary to the first retention feature 235 such that the first retention feature 235 can be engaged with the second retention feature 260 to securely attach the fluid dispenser 14 to the cap 12, and the second retention feature 260 can be disengaged to release the fluid dispenser 14 from the cap 12. It will be appreciated that the first retention feature 235 can include multiple arms that connect with the corresponding second retention feature 260, e.g., have hooks that snap, slide, or fit within or on the exterior surface of the second retention feature 260. It will also be appreciated that the first retention feature 235 and the second retention feature 260 can include other structures for engaging and disengaging the fluid dispenser, for example, the second retention feature 260 can include a plurality of slots or threads to allow engagement and rotation of the first retention feature 235 to secure attachment of the fluid dispenser 14 to the cap 12, or can include slots, tabs, flanges, detents, hooks, or any other suitable structure for retaining the first retention feature 235. The seal set 255 can include a first seal 255 on the periphery of the outer surface of the housing 240 of the cap 12 configured to seal with the inner surface of the shell housing 215, and a second seal 255 provided around the periphery of the cavity 245 for sealing the insert 255 when the insert 255 is inserted into the cavity 245 and support 250.

[0024] The cavity 245 and support 250 are adapted to receive an insert 225 for sterile transfer of fluid to and from the fluid container 1. For example, in one embodiment, the fluid dispenser 14 is configured such that after the cap 12 is connected to the fluid container 1 and fluid is transferred into the fluid container 1, at least a downward force toward the fluid container 1 allows the insert 225 to be inserted into the support 250 of the cavity 245 and disconnected from the body 205 of the fluid dispenser 14 to seal the fluid container, e.g., the insert 225 is press-fit into the cap 12 without requiring additional equipment or replacement of the cap 12. It will be appreciated that the insert 225 can also be sealed to the cap 12 using other structures for engaging / disengaging the insert 225, e.g., using a threaded connection system, engagements and recesses, ridges or protrusions, etc.

[0025] The sterile closure assembly 10, including the fluid dispenser 14 and the cap 12, may be made of the same or similar materials as the fluid container 1 and / or each other, or combinations thereof. In one embodiment, the fluid dispenser 14, including the body 205, shell housing 215, and insert 225, and the cap 12 may be made of polyolefins, such as, for example, but not limited to, polypropylene, high density polyethylene, linear low density polyethylene, etc. Other non-limiting examples of polymers suitable for making the various embodiments of the sterile closure assembly 10, including the cap 12 and the fluid dispenser 14, include fluoropolymers, polyesters, polycarbonates, and polyamides. It will be appreciated that these materials are examples, and that the actual materials of the cap 12 and the fluid dispenser 14 may vary within the principles of the present disclosure beyond the stated list, or may be a mixture of any of the above. In one embodiment, the material of the cap 12 is the same as the material of the fluid dispenser 14. In another embodiment, the material of the cap 12 can be different from the material of the fluid dispenser 14. In another embodiment, the materials of the various components of the fluid dispenser 14, for example, the body 205, the shell housing 215, and the insert 225, can be made of the same material or different materials, or combinations thereof.

[0026] The seals 220, 255 may be O-rings or gaskets formed from at least one or combination of silicone, fluoropolymer, ethylene vinyl acetate (EVA), thermoplastic, or other sealing, flexible and / or compressible biocompatible materials that are relatively inert, e.g., do not filter or significantly absorb, and are non-reactive with, medical, chemical, or biological fluids. Seals may also include quad rings or sealing thermoplastic or other flexible and / or compressible materials that are melt processed, e.g., overmolded or insert molded, to fill grooves in corresponding members with the thermoplastic or flexible material, and / or formed from any of the above materials.

[0027] The operation of the sterile closure assembly 10 with the fluid dispenser 14 and the connection / disconnection to the cap 12 is discussed below with reference to Figures 3A-3E. It is understood that the sterile closure assembly 10 can be used to transfer fluid to and from a fluid container, which can be either filling or removing fluid. For example, if the sterile closure assembly 10 is used to fill a fluid container, one of the fluid lines can be used to evacuate any gas in the fluid container, which is replaced as the fluid fills the fluid container. Alternatively, if the sterile closure assembly 10 is used to remove fluid from a fluid container, one of the fluid lines can be used to provide an inert gas, e.g., nitrogen or air, to induce a flow of fluid through the other fluid line 210, or a negative pressure system, such as a vacuum, can be used to remove fluid from the fluid container. As a non-limiting example, the transfer of fluid to fill a fluid container is discussed below.

[0028] 3A-3C show a fluid dispenser 14 connected to a cap 12 for transferring a fluid, e.g., a filling, into a fluid container 1, where the cap 12 is connected and secured to a rigid opening 2 of the fluid container 1. The fluid dispenser 14 is secured to the cap 12 via a retention mechanism (not shown) on the fluid dispenser 14 and the cap 12. As discussed above, initially, the opening 206 of the body 205 is sealed against the shell housing 215 between the seals 220, e.g., the first seal and the second seal, such that fluid cannot be dispensed from the fluid dispenser 14. Once the fluid dispenser 14 is connected to the cap 12 and capable of transferring fluid, the body 205 is urged in a downward direction toward the fluid container 1 such that the opening 206 of the body 205 is in fluid communication with the enlarged portion 230 of the shell housing 215. In this manner, as seen in Figures 3B and 3C, a second seal 220 is placed within the enlarged portion, thereby allowing fluid to be transferred, as shown by arrow F, through the fluid line 210 of the fluid dispenser 14, through the opening 206, through the enlarged portion 230, around the second end of the body 205 and the insert 225, into the cavity 245 and support 250, and into the fluid container 1. It will be appreciated that the fluid dispenser 14 can include a second fluid line 210 that can be used to transfer fluid and / or can be used as a vent that is routed counter to filling with fluid to allow for evacuating the fluid container 1 as the fluid displaces gas therein.

[0029] As seen in FIGS. 3D-3E, after completion of the transfer of fluid into the fluid container 1, the fluid dispenser 14 can be guided further down towards the fluid container 1 such that the insert 225 fits into the support 250 of the cavity 245. When the insert 225 is inserted into the cavity 245, the fluid container 1 is sealed by a seal 255 that engages the insert 225 at the opening of the cavity 245. As shown in FIG. 3E, the engagement force of the insert 225 into the cavity 245 is greater than the engagement force of the insert 225 into the second end of the body 205 due to, for example, the compressibility and / or elastic modulus of the seal, such that when the fluid dispenser 14 is disengaged from the cap 12, the insert 225 is disconnected from the second end of the body 205 and remains inserted into the cavity 245, sealing the fluid container 1 when the fluid dispenser 14 is disconnected from the cap 12. It will be appreciated that the fluid dispenser 14 may be configured such that when the seal 220 is pressed in a downward direction, the opening 206 can be sealed by sealing the second end of the body with the shell housing 215, or such that the body 205 can be moved in an upward direction such that the opening 206 is disengaged from the enlarged portion 230 and sealed between the first and second seals 220 and the shell housing 215. It will also be appreciated that the insert 225 can be engaged with the cavity 245 and / or the support 250 to seal the fluid container 1 using other removable or non-removable structures. For example, in one embodiment, the insert 225 may include a retention feature, such as a hook or protrusion or threaded connection, that engages a complementary retention feature of the cavity 245 and / or the support 250 to engage the insert 225 and disengage the insert 225 from the body 205. In another embodiment, the insert 225 may include a permanent retention feature, such as a hook structure that, when inserted into the cavity, is biased outwardly to engage complementary structure on the cavity 240 and / or support 250. In such a case, the sterile closure assembly cannot be used for multiple uses since the insert is permanently secured to the cap 12.

[0030] In another embodiment, as seen in Figures 4A and 4B, the sterile closure assembly 10 includes an insert 425 that is removable from the cavity 240 and / or support 250 of the cap 12. The sterile closure assembly 10 of Figures 4A and 4B has the same or similar features as the sterile closure assembly 10 discussed above with respect to Figures 2A and 2B, and components having the same or similar features will not be discussed in detail below. For example, as seen in Figure 4A, the second end of the body 205 includes an engagement piece 407, e.g., a hook piece, for engaging with a complementary engagement piece or member 426 of the insert 425. In one embodiment, the complementary engagement piece or member 426 of the insert 425 may include an opening that allows the engagement piece 407 of the body 205 to be inserted below the engagement piece or member 426 such that rotation of the body 205 of the fluid dispenser 14 causes the engagement piece 407 of the body 205 to engage with the complementary engagement piece or member 426 of the insert 425. In this case, as shown in FIG. 4B , when the insert 425 is inserted into and sealing the cap 12 of the fluid container 1, an upward force is applied to the body 205 of the fluid dispenser 14, causing the engagement piece 407 of the body 205 to engage with the complementary engagement piece or member 426 of the insert 425, such that the insert 425 can be removed from the cavity 245 and / or support 250, thereby allowing fluid to be transferred, e.g., filled or removed, from the fluid container 1. After completion of fluid transfer through the fluid container 1, the insert 425 can be removed, or as shown in Figure 4A, the insert 425 can be mated with the support 250 of the cavity 245 by directing the body 205 of the fluid dispenser 14 downwardly toward the fluid container 1 (as discussed above with respect to Figures 2A, 2B) and rotating the body 205 such that the engagement piece 407 of the body 205 is removed through the opening in the insert 425, thereby disengaging the insert 425 from the body 205. When the insert 425 is inserted into the cavity 245, the insert 425 and the seal 255 seal the opening in the cavity 245, thereby sealing the fluid container 1.It will be appreciated that in one embodiment, the seal 220 on the second end of the body 205 seals the body 205 against the insert 425 during fluid transfer, thereby preventing contamination of any contents on the top surface of the insert 425. It will also be appreciated that in one embodiment, a film, cap, valve, or similar sealing device that maintains a hermetic seal can be attached and / or coupled to the cap 12 of the fluid container and / or the fluid dispenser 14 for aseptic connection / disconnection of the fluid container. The film, cap, valve, or similar sealing device can then be pierced, removed, and / or rotated to allow for sterile fluid transfer when the fluid container is coupled to the fluid dispenser 14.

[0031] 5A and 5B are schematic and cross-sectional views of a sterile closure assembly 502 for a fluid container (e.g., fluid container 1 as discussed above) according to another embodiment. The sterile closure assembly 502 includes a cap 512 connectable to the fluid container and a fluid dispenser 514 configured to be joined together to form a sealed sterile fluid connection. The fluid dispenser 514 includes a fluid passageway through the body 505 and a fluid passageway through the sub-body 508 extending from an opening. The cap 512 is configured to sterilely connect the fluid passageway of the fluid dispenser 514 to the fluid container to provide fluid communication when the fluid dispenser 514 is connected to the cap 512, as discussed further below.

[0032] In this manner, the sterile closure assembly 502 is configured to connect and disconnect to a fluid container for aseptic transfer of fluid in a fluid container that can be used at temperatures as low as -85°C. It is appreciated that the sterile closure assembly 502 can be used at other temperatures, such as 0°C, room temperature, etc., while maintaining the benefits of the present disclosure. Thus, a fluid container having the sterile closure assembly 502 as discussed above is configured to be stored at freezing temperatures (e.g., temperatures below 0°C). In one embodiment, a fluid container having the sterile closure assembly 502 can also be heated and returned to ambient temperatures without any substantial deformation. Substantial deformation includes, for example, visible cracking of the material, shrinkage or expansion relative to its original shape at ambient temperatures that may interfere with or adversely affect the sealing of said connections. Low temperature elastic recovery testing can be performed according to ASTM D1329, ISO 2921, or any other suitable test method for identifying suitable shrinkage characteristics of a material at temperatures that may be used. The brittleness test can be carried out according to ASTM D2137, ISO 28702, or any other suitable test method for determining the resistance to cracking of a material at the temperatures that may be used.

[0033] The cap 512 can be connected to a rigid opening of the fluid container to secure the cap 512 to the fluid container. The cap 512 can be connected to the fluid container by a press fit of the cap 512 into the rigid opening, or the cap 512 and the rigid opening can include inter-engaging threads. It is appreciated that the cap 512 can also be connected to the fluid container 1 in other manners, such as using mechanical fasteners, such as clamps, corresponding engagement mechanisms, or welding or joining techniques, such as thermal bonding, impulse welding, laser welding, ultrasonic welding, or similar fusion / melting welding techniques. In one embodiment, the cap 512 can be connected to the fluid container using a tamper-evident connection system. For example, the cap 512 with the tamper-evident connection system can include inwardly biasing retention arms that engage corresponding protrusions around the rigid opening of the fluid container such that once the retention arms are pressed to a predetermined position on the rigid opening, the cap 512 cannot be easily removed from the fluid container without leaving visible signs of damage to the cap 512 and / or the fluid container. In another embodiment, the cap 512 with the tamper-evident connection system can include a protrusion on a lower portion of the threaded portion such that once the cap 512 is threaded to a predetermined position, the cap 512 cannot be removed from the fluid container 512, for example, by reversing the rotation of the cap 512 on the rigid opening. In yet another embodiment, the tamper-evident connection system can include a ring on the cap 512 that separates from the cap 512 when the cap 512 is removed from the fluid container. In this case, the tamper-evident connection system can alert a customer or user of a fluid container having cap 512 if the fluid container has been opened or attempted to be opened, and potentially contaminated and / or damaged.

[0034] The cap 512 includes a housing 540, a cavity 545 within the housing 540, a port 570, and a set of seals 255. The housing 540 of the cap 512 includes a second retention feature 560 having a shape complementary to the first retention feature 535 on the body 505 and sub-body 508 of the fluid dispenser 514 for engaging an outer surface of the housing 540 of the cap 512. The first retention feature 535 can engage with the second retention feature 560 to securely attach the liquid dispenser 514 to the cap 512, and can disengage to remove the liquid dispenser 514 from the cap 512. For example, in one embodiment, the second retention feature 560 can include a pin or protrusion that engages with a corresponding slot formed by the first retention feature 535 on the body 505 and sub-body 508 of the fluid dispenser 514. The insert 525 is configured to be engageable and disengageable with the port 570 to open and close a fluid communication channel between the fluid container and the port 570, as discussed further below. For example, in one embodiment, the fluid dispenser 514 is configured to engage the insert 525 after the cap 512 is connected to the fluid container such that a downward force toward the fluid container and rotation thereof can connect the insert 525 onto the fluid dispenser 514 and disconnect the insert 525 from the port 570 to allow the body 505 (and / or sub-body 508) of the fluid dispenser 514 to be inserted into the fluid container for sterile transfer of fluid to / from the fluid container. It will be appreciated that after fluid is transferred to the fluid container, the insert 525 can be re-engaged with the port 570 such that the insert 525 and seal 555 seal the port 570 from fluid communication with the fluid container.

[0035] For example, in one embodiment, as seen in Figures 6A, 6B, and 6C, cap 512 includes a housing 540, a cavity 545 within housing 540, a port 570 connected to the cavity, and a set of seals 555. Ports 570 each include a port shell 571 and an insert 525 connected to one end of port shell 571. Insert 525 is configured to be engageable and disengageable with port shell 571 to open and close a fluid communication channel between the fluid container and port 570, as discussed further below. For example, in one embodiment, insert 525 includes outer engagement pieces or members 527 spaced along a perimeter or circumference of insert 525 that are engageable with complementary outer engagement pieces or members 572 provided on an outer surface of port shell 571. In one embodiment, a space is provided between the outer engagement piece or member 527 and the complementary engagement piece or member 572 such that the insert 525 can be engaged and disengaged with the port shell 571 by rotating the insert 525 so that it is disposed within the corresponding space. It will be appreciated that when the insert 525 is engaged with the port shell 571, a seal 555 provided along an inner circumference of the outer engagement piece or member 527 seals the port 570 from fluid communication with the fluid container. It will be appreciated that the port 570 can be of the same or similar construction or can have a different construction as discussed below.

[0036] In another embodiment of the cap 512, as seen in Figures 7A, 7B, and 7C, the cap 512 includes a housing 740, a cavity 745 within the housing 740, a port 770 connected to the cavity, and a set of seals 720. The ports 770 each include a port shell 771 and an insert 725 connected to one end of the port shell 771. The insert 725 is configured to be engageable and disengageable with the port shell 771 to open and close a fluid communication channel between the fluid container and the port 770, as discussed further below. For example, in one embodiment, the insert 725 includes outer engagement pieces or members 727 spaced along the periphery or outer periphery of the insert 725 that are engageable with complementary outer engagement pieces or members 772 provided along an inner periphery of the port shell 771. In one embodiment, a space is provided between the outer engagement piece or member 727 and the complementary engagement piece or member 772 such that the insert 725 can be engaged and disengaged with the port shell 771 by rotating the insert 725 so that it is disposed within the corresponding space. It will be appreciated that when the insert 725 is engaged with the port shell 771, a seal 720 provided along the outer periphery of the insert 725 seals the port 770 from fluid communication with the fluid container. Although the inserts 525, 725 and the port shells 571, 771 have been discussed above as having outer engagement pieces and complementary engagement pieces or members, it will be appreciated that such disclosure is intended to be a non-limiting disclosure herein including other mechanical structures that allow the insert to be engageable and disengageable with the port. For example, a threaded connection or a snap fit can be used to engage and disengage the insert from the port.

[0037] Although the cap 512 is illustrated and shown as being a separate piece, it will be appreciated that such disclosure is not intended to be limiting. For example, the cap 512 can be constructed from ports that are connected to the housing, or the cap 512 can be constructed as a single molded piece or component. In that case, various inserts can be used to complement the mating pieces of the fluid dispenser. It will be appreciated that the port 570 can be a single port on the cap 512, in which case the port 570 is configured to allow connection to two separate fluid lines of a fluid dispenser connected thereto.

[0038] 5A and 5B, the fluid dispenser 514 includes a body 505 having a first end and a second end, a sub-body 508 having a first end and a second end, a fluid line 510 connected to the body 505 and the sub-body 508, a shell housing 515 disposed about the body 505, a sub-housing 509 disposed about the sub-body 508, and a set of seals 520. The body 505 and the sub-body 508 each include an opening 506 near the second end that is fluidly connected to the fluid line 510 and configured to be in fluid communication with a fluid container when the fluid dispenser 514 is connected to the cap 512. In one embodiment, the shell housing 515 and the sub-housing 509 of the fluid dispenser 514 each include a first retention mechanism 535 for engaging an outer surface of the housing 540 of the cap 512, as discussed above. The shell housing 515 includes a collapsible structure to allow the fluid line 510 to be inserted into a fluid container while maintaining sterility of the fluid line 510. For example, in one embodiment, the shell housing 515 includes an accordion-like structure having bellows that fold and expand to allow compression and expansion of the shell housing 515 as the fluid line 510 moves in and out of the shell housing 515, such as when the fluid line 510 is used as a dip tube to be inserted into a fluid container. It will be appreciated that other collapsible structures can be used, such as a sliding shell with a seal within the shell housing, or similar structures that allow for sterile fluid communication with a fluid container. The secondary body 508 can have the same or similar structure as the main body 505, and in one embodiment, the secondary body 508 includes a secondary shell housing 509 around the secondary body 508 that only partially allows movement of the fluid line 510 into the fluid container by rotation of the secondary body 508, such as not being structured as a dip tube and only allowing partial insertion into the fluid container.

[0039] The fluid line 510 may include a tube connector toward the first end of the main body 505 and the sub-body 508 for connection to a fluid transfer system for transfer of fluid to, e.g., filling or removing from, a fluid container. The tube connector may be selected from the group consisting of a hose barb, an overmolded connection, a threaded connection, a press-fit connection, a snap-fit ​​connection, or combinations thereof. It will be appreciated that the tube connector may also be formed contiguously with the fluid transfer system, for example, by molding or overmolding the fluid dispenser together with the fluid transfer system.

[0040] In one embodiment, the fluid dispenser 514 including the body 505 and the sub-body 508 includes an engagement piece 507, e.g., a protrusion having a shape that matches a complementary engagement member 526, 726 (as shown in FIGS. 6B, 7B ) of an insert 525, 725 on the second end of the body 505 and the sub-body 508. For example, the engagement member 526, 726 includes an opening that can receive the engagement piece 507 of the body 505 and / or the sub-body 508 such that rotation of the body 505 and / or the sub-body 508 of the fluid dispenser 514 causes the engagement piece 507 of the body 505 and / or the sub-body 508 to engage with the complementary engagement piece or member 526, 726 of the insert 525, 725. In response, when a downward rotational force is applied to the body 505 and / or sub-body 508 of the fluid dispenser 514, the engagement pieces 507 of the body 505 and / or sub-body 508 engage the complementary engagement members 526, 726 of the insert 525, 725 such that further rotation of the body 505 and / or sub-body 508 rotates the insert 525, 725 to disengage the insert 525, 725 from the port 570. The insert 525, 725 is then inserted into a fluid container such that fluid can be transferred, e.g., filled or removed, from the fluid container. After completion of fluid transfer with the fluid container, the insert 525, 725 can be directed upwardly towards the port 570 such that the insert 525, 725 can be rotated to engage and seal the port 570. Upon insertion of the insert 525, 725 into the cavity 545 and port 570, the insert 525, 725 and seal 555 seal the port 570, thereby sealing the fluid container. It is also appreciated that in one embodiment, a film, cap, valve, or similar sealing device that maintains a hermetic seal can be attached and / or coupled to the cap 512 and / or port 570 of the fluid container and / or the fluid dispenser 514 for aseptic connection / disconnection of the fluid container. The film, cap, valve, or similar sealing device can then be pierced, removed, and / or rotated to further enable transfer of sterile fluid when the fluid dispenser 514 is coupled to the fluid container.

[0041] The sterile closure assembly 502 including the fluid dispenser 514 and the cap 512 may be made of the same or similar materials as the container and / or each other, or combinations thereof. In one embodiment, the fluid dispenser 514 including the body 505, the sub-body 508, the shell housing 515, the sub-shell housing 509, and the insert 525, as well as the cap 512 may be made of polyolefins, such as, but not limited to, polypropylene, high density polyethylene, linear low density polyethylene, and the like. Other non-limiting examples of polymers suitable for making the various embodiments of the sterile closure assembly 502 including the cap 512 and the fluid dispenser 514 include fluoropolymers, polyesters, polycarbonates, and polyamides. It will be appreciated that these materials are examples, and that the actual materials of the cap 512 and the fluid dispenser 514 may vary beyond the stated list and may be a mixture of any of the above within the principles of the present disclosure. In one embodiment, the material of the cap 512 is the same as the material of the fluid dispenser 514. In another embodiment, the material of the cap 512 can be different from the material of the fluid dispenser 514. In another embodiment, the materials of the various components of the fluid dispenser 514, such as the body 505, the sub-body 508, the shell housing 515, the sub-shell housing 509, and the insert 525, can be made of the same material or different materials, or combinations thereof. In one embodiment, the shell housing 515 can be made of silicone or a flexible polymer to allow for compression and expansion of the shell housing.

[0042] The seals 520, 555 may be O-rings or gaskets formed from at least one or combination of, but not limited to, silicone, fluoropolymer, ethylene vinyl acetate (EVA), thermoplastic, or other sealing, flexible and / or compressible biocompatible materials that are relatively inert, e.g., do not filter or significantly absorb medical or biological fluids, and are non-reactive. Seals may also include quad rings or sealing thermoplastic or other flexible and / or compressible materials that are melt processed, e.g., overmolded or insert molded, to fill grooves in corresponding members with the thermoplastic or flexible material, and / or formed from any of the above materials.

[0043] Operation of the fluid dispenser 514 and its connection / disconnection to the cap 512 is discussed below with reference to Figures 8A-9C. It will be appreciated that any of the inserts or ports and related structures discussed above may be used, but are discussed below with respect to insert 525 as a non-limiting example.

[0044] 8A and 8B show a body 505 of a fluid dispenser 514 connecting to a cap 512 for transferring a fluid, e.g., a filler, into a fluid container, where the cap 512 is connected and secured to a rigid opening of the fluid container. The body 505 of the fluid dispenser 514 is secured to the cap 512 by rotating a first retention feature 535 of the fluid dispenser 514 onto a second retention feature 560 on a port 570 of the cap 512. Initially, the opening 506 of the body 505 is sealed against the shell housing 515 by the seals 520, e.g., between a first seal and a second seal, such that fluid cannot be dispensed from the body 505 of the fluid dispenser 514. Once the body 505 of the fluid dispenser 514 is connected to the cap 512 and ready to transfer fluid, the body 505 is urged in a downward direction towards the fluid container and rotated so that the engagement piece 507 on the body 505 engages with a complementary engagement member 526 of the insert 525. After the body 505 and the insert 525 are engaged, the body 505 is further rotated so that the outer engagement piece 527 disengages from the complementary engagement piece or member 572 of the port 570, thereby allowing the fluid line 510 and the insert 525 to be inserted into the fluid container such that a sterile fluid communication channel is formed between the fluid dispenser 514 and the fluid container.

[0045] For example, as seen in Figures 8C and 8D, the fluid line 510 and insert 525 can be guided downwards towards the fluid container 501 so that the opening 506 is no longer located between the seal 520 and the shell housing (not shown). The opening 506 and insert 525 can then be displaced to different heights within the fluid container 501 for transfer of fluid to / from the fluid container 501, e.g., as a dip tube that can be lowered (or raised) near the fluid level to prevent foaming or allow fluid to be drained. In one embodiment, when the opening 506 and insert 525 are displaced into the fluid container 501, the shell housing (e.g., shell housing 515 having an accordion-like structure with bellows) can be folded and expanded to allow compression and expansion of the shell housing and insertion of the fluid line 510 into the fluid container. In this way, the outer surface of the fluid line 510 can be maintained in a sterile state since it only comes into contact with the inner surface of the shell housing and the fluid within the fluid container 501. It will also be appreciated that such a structure allows for automatic filling or removal of fluid from the fluid container 501 since the fluid line 510 can be lowered (or raised) at different heights. For example, the shell housing and / or the fluid line (if the shell housing is transparent) may include index marks or measurements to indicate the depth of the fluid line into the fluid container 501. In this case, the insertion depth of the fluid line 510 can be controlled for filling and / or removing fluid from the fluid container 501.

[0046] After the fluid transfer step is completed, the opening 506 and the insert 525 can be raised in an upward direction such that the opening 506 is located between the seal 520 and the shell housing 515, and the insert 525 can be rotated to engage the port 570. It can be appreciated that when the insert 525 is engaged with the port shell 570, a seal 555 along the inner circumference of the outer engagement piece or member 527 seals the port 570 from fluid communication with the fluid container 501. Further rotation of the body 505 disengages the engagement piece 507 on the body 505 with the complementary engagement member 526 of the insert 525. Thus, the fluid dispenser 514 can be removed from the cap 512 and fluid container 501 by rotating the fluid dispenser 514 such that the first retention feature 535 of the body 505 of the fluid dispenser disengages with the second retention feature 560 on the port 570 of the cap 512. It will be appreciated that because the insert 525 only contacts the fluid dispenser 514 for the transfer of fluid to and from the fluid container 501, there is no need for a secondary step to seal the fluid container 501, such as replacing a sterile closure assembly and stopper, which would make the fluid processing system susceptible to contamination, and therefore the fluid processing system remains closed.

[0047] Similarly, as seen in FIG. 8D, the secondary body 508 of the fluid dispenser 514 can be connected to the cap 512 by rotating the first retention feature 535 onto the second retention feature 560 on the port 570 of the cap 512. For example, as seen in FIGS. 9A-9B, initially, the opening 506 of the secondary body 508 is sealed to the secondary shell housing 509 between the seals 520, e.g., the first and second seals, such that fluid cannot be transferred through the secondary body 508 of the fluid dispenser 514. Once the fluid dispenser 514 is connected to the cap 512 and ready to transfer fluid, the secondary body 508 can be urged in a downward direction toward the fluid container 501 and rotated such that the engagement piece 507 on the secondary body 508 engages the complementary engagement member 526 of the insert 525. After the sub-body 508 and the insert 525 are engaged, the sub-body 508 is further rotated such that the outer engagement piece 527 disengages from the complementary engagement piece or member 572 of the port 570, thereby allowing the fluid line 510 and the insert 525 to be inserted into the fluid container such that a fluid communication channel is formed between the sub-body 508 of the fluid dispenser 514 and the fluid container.

[0048] 9B, the fluid line 510 and insert 525 can be directed downwardly towards the fluid container 501 such that the opening 506 is no longer located between the seal 520 and the secondary housing 509. The opening 506 and insert 525 can then be displaced within the fluid container 501 below the cap 512 for transfer of fluid to / from the fluid container 501. In one embodiment, when the opening 506 and insert 525 are displaced into the fluid container 501, the secondary shell housing 509 allows the fluid line 510 to move at least partially into the fluid container 510 such that a portion of the outer surface of the fluid line 510 is not exposed to the environment and sterility of the fluid is maintained.

[0049] After the fluid transfer process is completed, the opening 506 and insert 525 can be raised in an upward direction such that the opening 506 is located between the seal 520 and the secondary shell housing 509, and the insert 525 can be rotated to engage the port 570. It can be appreciated that when the insert 525 is engaged with the port shell 570, the seal 555 along the inner circumference of the outer engagement piece or member 527 seals the port 570 from fluid communication with the fluid container 501. Further rotation of the secondary body 508 disengages the engagement piece 507 on the secondary body 508 from the complementary engagement member 526 of the insert 525. Thus, by rotating the secondary body 508 of the fluid dispenser 514, the first retention feature 535 of the secondary housing shell 509 disengages with the second retention feature 560 on the cap 512, allowing the fluid dispenser 514 to be removed from the cap 512 and fluid container 501. It will be appreciated that because the insert 525 only contacts the fluid dispenser 514 for transfer of fluid to and from the fluid container 501, there is no need for a secondary step to close the fluid container 501, such as replacement of a sterile closure assembly, stopper, or the like, which would render the fluid processing system susceptible to contamination, and therefore the fluid processing system remains closed.

[0050] Another embodiment of the sub-body and the second port is shown in Figures 10A-10B. In this embodiment, the second port 1070 has a different structure than the first port (e.g., port 570 as discussed above) and the sub-body 1008 has a different structure than the sub-body 508. For example, in one embodiment, the cap 1012 includes a first cavity and a first port (e.g., cavity 545 and port 570 as shown in Figures 5A-9B), a second cavity 1045 and a second port 1070 connected to the second cavity 1045. The second port 1070 includes a second shell 1071, a second insert 1025 disposed to seal one end of the second port 1070, and a first spring 1080 biasing the second insert 1025 to a closed position, e.g., an upward position away from the fluid container. The fluid dispenser includes a secondary body 1008 having a second shell housing 1009, a sealing end 1013 disposed within the second shell housing 1009, a second spring 1011 within the second shell housing 1009 biasing the sealing end 1013 toward the opening 1006 of the secondary body 1008, and a third set of seals 1020. The second shell housing 1009 is configured to engage an outer surface of the second port 1070 such that connection of the second shell housing 1009 to the second port 1070 causes the secondary body 1008 to bias the insert 1025 toward the fluid container to provide a second fluid communication channel between the secondary body 1008 and the fluid container.

[0051] 10A, initially, the opening 1006 of the secondary body 1008 is sealed to the secondary shell housing 1009 between the seal 1020, e.g., the first seal, and the sealing end 1013, such that fluid cannot be transferred through the fluid dispenser secondary body 1008. Once the fluid dispenser secondary body 1008 is connected to the cap 1012 and is ready to transfer fluid, the sealing end 1013 is biased away from the second end of the secondary body 1008 to open the fluid communication channel of the opening 1006. The secondary body 1008 can also be rotated such that it is forced in a downward direction toward the fluid container, biasing the insert 1025 toward the fluid container such that a fluid communication channel is formed between the opening 1006 of the fluid dispenser secondary body 1008 and the fluid container. For example, in one embodiment, a downward force towards the fluid container biases the sealing end 1013 against the second shell housing 1009 such that the opening 1006 is in fluid communication with the port 1070. The second end of the sub-body 1008 engages the insert 1025, which then causes the downward force to displace the insert 1025 relative to the port 1070 such that fluid can flow around the insert 1025 and into the fluid container.

[0052] After the fluid transfer step is completed, the opening 1006 and insert 1025 can be rotated such that the spring 1080 biases the insert 1025 to a closed position. The insert 1025 is engaged with the second port 1070 such that the seal 1055 and insert 1025 seal the port 1070 from fluid communication with the fluid container. Further rotation of the secondary body 1008 disengages the second shell housing 1009 from the second port 1070 and the spring 1011 biases the sealing end 1013 towards the second end of the secondary body 1008 such that the opening 1006 is located between the seal 1020 and the sealing end 1013 of the secondary body 1008. It will be appreciated that because the insert 1025 only contacts the fluid dispenser sub-body 1008 for transfer of fluid to and from the fluid container, there is no need for a secondary step to close the fluid container, such as replacing a sterile closure assembly and stopper, which would make the fluid processing system susceptible to contamination, and therefore the fluid processing system remains closed.

[0053] It is appreciated that in one embodiment, the second port 1070 forms a fluid connection with the fluid container such that when the insert is forced in a downward direction, a fluid communication channel is formed directly with the fluid container. In another embodiment, as seen in Figures 11A, 11B, the second port 1070 includes a pipe with an angled design, e.g., a J-tube design, so that the fluid is directed to the side of the fluid container. The J-tube can be press-fitted into the port or mechanically attached, e.g., with screws, bolts, etc. The angled pipe design avoids bubbling of the fluid during filling by directing the fluid to the side of the fluid container so that the fluid flows down the side of the fluid container. 11A, 11B further illustrate that the ports 570, 1070 can have different designs, such as where the body 505 of the fluid dispenser 514 connects to a first port 570, and the secondary body 1008 of the fluid dispenser 514 connects to a second port 1070 for transfer of fluid into the fluid container 501. It will be appreciated that the ports of the cap can be the same or different designs depending on the application and are not limited to the designs discussed above.

[0054] In another embodiment, a method for sterilely transferring fluid into or out of a fluid container for freeze / thaw applications is provided. With reference to Figures 5A and 5B, the method includes connecting a cap 512 to an opening of the fluid container. The cap 512 includes a housing 540, a cavity 545 in the housing 540, a port 570 connected to the cavity 545, and a set of seals 555. The ports 570 each include a port shell 571 and an insert 525 connected to one end of the port shell 571, the insert 525 configured to open and close a fluid communication channel between the fluid container and the port 570. The method further includes transferring fluid into the fluid container by aseptically connecting and disconnecting a fluid dispenser 514 to an outer surface of the port shell 571. The fluid dispenser 514 may include a body 505 having a first end and a second end, a sub-body 508 having a first end and a second end, a fluid line 510 connected to the body 505, a shell housing 515 disposed around the body 505, a second set of seals, a sub-shell housing 509 disposed around the sub-body 508, and an engagement piece 507 on the body 505 and the sub-body 508 that is engageable with the insert 525, such that when the engagement piece 507 of the fluid dispenser is engaged with the insert 525 of the port 570 by rotational engagement, the fluid line 510 together with the insert 525 may be directed downwardly towards the fluid container to open a fluid communication channel with the fluid container so that fluid may be transferred, e.g., filled or removed, from the fluid container. After completion of fluid transfer with the fluid container, the insert 525 may be directed upwardly towards the port 570 so that the insert 525 may be rotated to engage and seal the port 570. When insert 525 is inserted into cavity 545 and port 570, insert 525 and seal 555 seal against port 570, thereby sealing the fluid container.

[0055] The fluid container can then be stored, transported, and used during the manufacturing process. For example, in one embodiment, the fluid container can be frozen such that the transferred fluid in the fluid container is frozen at approximately -85°C. The fluid container can then be transported and the transferred fluid can be thawed at a temperature of approximately 1°C to 10°C to allow for fluid flow. The fluid dispenser 514 can then be used for sterile connection and disconnection to the fluid container. For example, in one embodiment, the body 505 of the fluid dispenser 14 can be rotated within the shell housing, and the shell housing 515 can be compressed such that the fluid line 510 is sterile inserted into the fluid container. Once the sub-body 508 is attached to the cap 512, a vacuum system (or positive pressure) can be used to remove fluid from the fluid container through the fluid line in the body 508.

[0056] Aspects Any of the embodiments 1 to 11 can be combined with any of the embodiments 12 to 17 and / or 18 to 19 and / or 20, and vice versa.

[0057] Aspect 1: A sterile closure assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap comprising a housing, a cavity within the housing having a support, and a first set of seals; and a fluid dispenser connectable to an outer surface of the housing of the cap, the fluid dispenser comprising a body having a first end and a second end, a fluid line within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an insert connectable to the second end of the body, the body including an opening near the second end that is connected to the fluid line and is configured to be in fluid communication with the fluid container when the fluid dispenser is connected to the cap, the fluid dispenser being configured such that a downward force towards the fluid container causes the insert to engage with the support of the cavity and the insert to disconnect from the body of the fluid dispenser to seal the fluid container.

[0058] Aspect 2. The sterile closure assembly of aspect 1, wherein the fluid container is a bottle.

[0059] Aspect 3: A sterile closure assembly according to any one of aspects 1 to 2, wherein the shell housing includes an enlarged portion in fluid communication with the opening, such that when fluid is supplied or removed through the fluid line of the fluid dispenser, fluid flows from the opening through the enlarged portion, around the insert, into the fluid container, or from the fluid container, around the insert, through the enlarged portion and then through the opening.

[0060] Aspect 4: A sterile closure assembly according to any one of aspects 1 to 3, wherein the insert is disconnected from the body by a press fit into the cavity and support, and / or connected by rotating the fluid dispenser while the insert is fitted into the support of the cavity.

[0061] Aspect 5. A sterile closure assembly as described in Aspect 4, wherein the first set of seals comprises a first seal around an outer surface of the cap connectable to an inner surface of the shell housing, and a second seal around the cavity.

[0062] Aspect 6: A sterile closure assembly according to any one of aspects 1 to 5, wherein the second set of seals comprises a third seal disposed on the body above the opening and a fourth seal disposed along the length of the body below the opening, and wherein the third seal and the fourth seal engage with the shell housing when the opening is located above the enlarged portion.

[0063] Aspect 7 A sterile closure assembly described in any one of Aspects 1 to 6, wherein the shell housing has a plurality of first retention features extending from one end of the shell housing configured to engage with second retention features provided on an outer surface of the cap housing, the first retention features and second retention features having complementary shapes.

[0064] Aspect 8. A sterile closure assembly according to any one of aspects 1-7, wherein the first set of seals and the second set of seals comprise one or more of silicone and ethylene vinyl acetate (EVA).

[0065] Aspect 9. The sterile closure assembly of any one of aspects 1-8, wherein at least one of the cap or the insert comprises a fluoropolymer.

[0066] Aspect 10. A sterile closure assembly according to any one of aspects 1 to 8, wherein the cap is connected to the fluid container using a tamper-evident connector.

[0067] Aspect 11: A sterile closure assembly as described in aspect 4, wherein the fluid dispenser has an engagement piece for engaging with the insert or an engagement member by which the fluid dispenser can engage with the insert so that the insert can be removed from the support of the cavity by rotating the fluid dispenser.

[0068] Aspect 12. A sterile closure assembly as described in any one of aspects 1 to 11, wherein the shell housing has a plurality of arms extending from one end thereof configured to engage with a corresponding plurality of slots provided on an outer surface of the cap housing, the arms and slots having complementary shapes such that they can engage and disengage.

[0069] Aspect 13. A sterile closure assembly according to any one of aspects 1-11, further comprising means for engaging and disengaging the cap with the fluid dispenser.

[0070] Aspect 14. A sterile closure assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap comprising a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals, the port comprising a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port; and a fluid dispenser connectable to an outer surface of the port shell, the fluid dispenser comprising a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an engagement piece engageable with the insert, the engagement piece of the fluid dispenser being engageable with the insert of the port by rotational engagement such that the fluid line can be directed downwardly toward the fluid container together with the insert so that the fluid communication channel with the fluid container is opened.

[0071] Aspect 15: A sterile closure assembly for a fluid container as described in Aspect 14, wherein the cap comprises a second cavity and a second port connected to the second cavity, the second port comprising a second shell, a second insert configured to seal one end of the second port, and a first spring configured to bias the second insert into a closed position.

[0072] Aspect 16. A sterile closure assembly for a fluid container as described in aspect 15, further comprising a fluid dispenser sub-body having a second shell housing, a second spring biasing the sub-body within the second shell housing, and a third set of seals, wherein the second shell housing is configured to engage an outer surface of the second port such that connection of the second shell housing to the second port causes the sub-body to bias the insert toward the fluid container to provide a second fluid communication channel between the sub-body and the fluid container.

[0073] Aspect 17. A sterile closure assembly for a fluid container according to aspect 16, further comprising a pipe connected to the second port configured to direct fluid to a side of the fluid container.

[0074] Aspect 18. A sterile closure assembly for a fluid container according to aspect 17, wherein the sub-body comprises a tube connector selected from the group consisting of a hose barb, an overmolded connection, a threaded connection, a press-fit connection, a snap-fit ​​connection, or a combination thereof.

[0075] Embodiment 19. A sterile closure assembly for a fluid container according to any one of embodiments 14-18, wherein the shell housing comprises a compressible bellows to allow for sterile insertion of a fluid line into the fluid container.

[0076] Aspect 20: A method for sterile transfer of fluid into or out of a fluid container, comprising the steps of: connecting a cap to an opening of the fluid container, the cap comprising a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals, the port comprising a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port; and aseptically connecting and disconnecting a fluid dispenser to an exterior surface of the port shell. and transferring fluid into the fluid container by rotating the fluid dispenser such that the fluid dispenser comprises a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an engagement piece engageable with the insert, wherein when the engagement piece of the fluid dispenser is engaged with the insert of the port by rotational engagement, the fluid line can be directed downwardly toward the fluid container together with the insert such that a fluid communication channel with the fluid container is opened.

[0077] Aspect 21 The method of aspect 20, further comprising the steps of freezing the transferred fluid in the fluid container at approximately -85°C, thawing the transferred fluid at a temperature of approximately 1°C to 10°C to enable fluid flow, aseptically connecting and disconnecting the fluid dispenser to the fluid container, rotating the fluid line within a shell housing of the fluid dispenser and compressing the fluid dispenser so that the fluid line is sterilely inserted into the fluid container, and removing fluid from the fluid container through the fluid line.

[0078] Aspect 22: A fluid dispenser connectable to an outer surface of a cap of a fluid container, the fluid dispenser comprising: a body having a first end and a second end, the body including a fluid line disposed between the first end and the second end; and a shell housing disposed around the body, the fluid line at the second end of the body configured to be connectable with an insert disposed in the cap by rotating the body, the shell housing including a compressible bellows portion to enable sterile insertion of the fluid line into the fluid container.

[0079] The examples disclosed herein are to be considered in all respects as illustrative and not restrictive. The scope of the invention is indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

1. 1. A sterile closure assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap comprising a housing, a cavity in the housing having a support, and a first set of seals; a fluid dispenser connectable to an outer surface of the housing of the cap, the fluid dispenser comprising a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed about the body, a second set of seals, and an insert connectable to the second end of the body; Equipped with the body includes an opening near the second end that is connected to the fluid line and that is configured to be in fluid communication with the fluid container when the fluid dispenser is connected to the cap; The fluid dispenser is configured such that a downward force toward the fluid container causes the insert to engage with the support of the cavity and disconnect the insert from the body of the fluid dispenser to seal the fluid container. A sterile closure assembly.

2. The sterile closure assembly of claim 1 , wherein the fluid container is a bottle.

3. 2. The sterile closure assembly of claim 1, wherein the shell housing includes an enlarged portion in fluid communication with the opening, such that when fluid is supplied or removed through the fluid line of the fluid dispenser, the fluid flows from the opening through the enlarged portion, around the insert, into the fluid container, or from the fluid container, around the insert, through the enlarged portion and then through the opening.

4. 2. The sterile closure assembly of claim 1, wherein the insert is disconnected from the body by a press fit into the cavity and the support and / or connected by rotating the fluid dispenser while the insert is fitted into the support of the cavity.

5. 5. The sterile closure assembly of claim 4, wherein the first set of seals comprises a first seal around the outer surface of the cap connectable to an inner surface of the shell housing and a second seal around the cavity.

6. 2. The sterile closure assembly of claim 1, wherein the second set of seals comprises a third seal disposed on the body above the opening and a fourth seal disposed along the length of the body below the opening, the third seal and the fourth seal engaging the shell housing when the opening is located above the enlarged portion.

7. 2. The sterile closure assembly of claim 1, wherein the shell housing comprises a plurality of first retention features extending from one end of the shell housing configured to engage with second retention features on the outer surface of the housing of the cap, the first retention features and the second retention features having complementary shapes.

8. The sterile closure assembly of claim 1 , wherein the first set of seals and the second set of seals comprise one or more of silicone and ethylene vinyl acetate (EVA).

9. The sterile closure assembly of claim 1 , wherein at least one of the cap or the insert comprises a fluoropolymer.

10. 10. The sterile closure assembly of claim 1, wherein the cap is connected to the fluid container with a tamper-evident connector.

11. The sterile closure assembly of claim 4, wherein the fluid dispenser has an engagement piece for engaging with the insert or an engagement member by which the fluid dispenser can engage with the insert so that the insert can be removed from the support of the cavity by rotating the fluid dispenser.

12. 2. The sterile closure assembly of claim 1, wherein the shell housing comprises a plurality of arms extending from one end thereof configured to engage with a corresponding plurality of slots in the outer surface of the housing of the cap, the arms and the slots having complementary shapes to enable engagement and disengagement therebetween.

13. 10. The sterile closure assembly of claim 1, further comprising means for engaging and disengaging the cap with the fluid dispenser.

14. 1. A sterile closure assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap comprising a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals; the port comprises a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port; a fluid dispenser connectable to an exterior surface of the port shell, the fluid dispenser comprising: a body having a first end and a second end; a fluid line disposed within the body between the first end and the second end; a shell housing disposed about the body; a second set of seals; and an engagement piece engageable with the insert; a fluid dispenser, the engagement piece of which is engageable with the insert of the port by rotational engagement so as to direct the fluid line together with the insert downwardly towards the fluid container so that the fluid communication channel with the fluid container is open; 1. A sterile closure assembly for a fluid container comprising:

15. 15. The sterile closure assembly for a fluid container of claim 14, wherein the cap comprises a second cavity and a second port connected to the second cavity, the second port comprising a second shell, a second insert provided to seal one end of the second port, and a first spring biasing the second insert to a closed position.

16. 16. The sterile closure assembly for a fluid container of claim 15, further comprising a sub-body of the fluid dispenser having a second shell housing, a second spring biasing the sub-body within the second shell housing, and a third set of seals, wherein the second shell housing is configured to engage an outer surface of the second port such that connection of the second shell housing to the second port causes the sub-body to bias the insert toward the fluid container to provide a second fluid communication channel between the sub-body and the fluid container.

17. 17. A sterile closure assembly for a fluid container according to claim 16, further comprising a pipe connected to the second port configured to direct fluid to a side of the fluid container.

18. 20. The sterile closure assembly for a fluid container of claim 17, wherein the sub-body comprises a tubing connector selected from the group consisting of a hose barb, an overmolded connection, a threaded connection, a press-fit connection, a snap-fit ​​connection, or combinations thereof.

19. 15. The sterile closure assembly for a fluid container of claim 14, wherein the shell housing includes a compressible bellows to allow for sterile insertion of the fluid line into the fluid container.

20. 1. A method for the sterile transfer of a fluid into or out of a fluid container, comprising: connecting a cap to an opening of the fluid container, the cap comprising a housing, a cavity in the housing, a port connected to the cavity, and a first set of seals, the port comprising a port shell and an insert connected to one end of the port shell, the insert configured to open and close a fluid communication channel between the fluid container and the port; transferring fluid into the fluid container by aseptically connecting and disconnecting a fluid dispenser to an outer surface of the port shell, the fluid dispenser comprising a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a shell housing disposed around the body, a second set of seals, and an engagement piece engageable with the insert, the engagement piece of the fluid dispenser being capable of directing the fluid line together with the insert downwardly toward the fluid container such that the fluid communication channel with the fluid container is open when the engagement piece of the fluid dispenser is engaged with the insert of the port by rotational engagement; A method comprising:

21. freezing the transferred fluid in the fluid container at approximately -85°C; thawing the transferred fluid at a temperature of about 1° C. to 10° C. to allow for flow of the fluid; aseptically connecting and disconnecting the fluid dispenser to the fluid container; rotating the fluid line within the shell housing of the fluid dispenser and compressing the fluid dispenser such that the fluid line is sterilely inserted into the fluid container; removing the fluid from the fluid container through the fluid line; 21. The method of claim 20, further comprising:

22. 1. A fluid dispenser connectable to an exterior surface of a cap of a fluid container, comprising: a body having a first end and a second end, the body including a fluid line disposed between the first end and the second end; a shell housing provided around the main body; Equipped with A fluid dispenser, wherein the fluid line at the second end of the body is configured to be connectable with an insert provided in the cap by rotating the body, and the shell housing includes a compressible bellows portion to enable sterile insertion of the fluid line into the fluid container.

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