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

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 the benefit of priority of U.S. Provisional Application No. 63 / 303,016, filed Jan. 25, 2022, which is incorporated herein by reference.

[0002] This disclosure generally relates to a system for aseptically transferring fluid from a fluid container. More particularly, this disclosure relates to an aseptic closure assembly, method, and components for aseptically transferring fluid from a fluid container, including a cap and a fluid dispensing assembly.

Background Art

[0003] In chemical and / or biological processes, process materials may be utilized or produced, which are stored in storage containers containing pharmaceutical fluids or biological fluids, acids, solvents, bases, photoresists, dopants, inorganic solutions, organic solutions, etc., such as bags for bioprocesses having a robust connection system, bottles, etc. The process materials may, in some cases, need to be frozen or otherwise kept at low temperatures within the storage container. When using such fluids, the storage container needs to properly contain the chemicals during storage, transportation, and ultimately during the manufacturing process itself. However, currently, in methods and fluid transfer assemblies for transferring fluid between storage containers having a robust connection system, the sterility of the system cannot be guaranteed.

Summary of the Invention

[0004] This disclosure generally relates to a system for aseptically transferring fluid from a fluid container. More particularly, this disclosure relates to an aseptic closure assembly, method, and components for aseptically transferring fluid from a fluid container, including a cap and a fluid dispensing assembly.

[0005] In one embodiment, an aseptically sealed assembly for a fluid container is provided. The aseptically sealed assembly is a cap connectable to the opening of a fluid container, and includes a cap having a housing, a cavity within the housing having a support, and a first set of seals, and a fluid dispenser connectable to the outer surface of the housing of the cap. The fluid dispenser includes a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided 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, which is connected to the fluid line and configured to communicate with the fluid container when the fluid dispenser is connected to the cap. Furthermore, the fluid dispenser is configured such that a downward force toward the fluid container causes the insert to engage with the support in the cavity, disconnecting the insert from the body of the fluid dispenser and sealing the fluid container.

[0006] In another embodiment of the present invention, a sterile closure assembly is provided, comprising a cap connectable to the opening of a fluid container, the cap comprising a housing, a cavity within 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, configured to open and close a fluid communication channel between the fluid container and the port, and a fluid dispenser connectable to the outer surface of the port shell. The fluid dispenser comprises a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided around the body, a second set of seals, and an engaging piece that can engage with the insert. The engaging piece of the fluid dispenser is engageable with the insert of the port by rotational engagement so that the fluid line can be guided downward toward the fluid container together with the insert so that a fluid communication channel with the fluid container is opened.

[0007] In one embodiment, a method is provided for aseptically transferring fluid into or from a fluid container. The method includes the step of connecting a cap to the opening of a fluid container, wherein the cap includes a housing, a cavity within 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 being configured to open and close a fluid communication channel between the fluid container and the port. The method further includes the step of transferring fluid into the fluid container by aseptically connecting and disconnecting a fluid dispenser to the outer surface of the port shell. The fluid dispenser includes a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided around the body, a second set of seals, and an engaging piece that can engage with the insert. When the engaging piece of the fluid dispenser engages with the port insert by rotational engagement, the fluid line can be guided downward toward the fluid container together with the insert, so that a fluid communication channel with the fluid container opens.

[0008] In yet another embodiment, a fluid dispenser is provided that can be connected to the outer surface of the cap of a fluid container. The fluid dispenser includes a body having a first end and a second end, with a fluid line provided between the first end and the second end, and a shell housing provided around the body. The fluid line at the second end of the body is configured to be connectable to an insert provided in the cap by rotating the body, and the shell housing includes a compressible bellows section that allows for sterile insertion of the fluid line into the fluid container. [Brief explanation of the drawing]

[0009] [Figure 1] This is a schematic diagram of a sterile closed assembly according to one embodiment. [Figure 2A] Figures 2A and 2B are exploded views and perspective views of the cap and fluid dispenser according to Figure 1. [Figure 2B] Figures 2A and 2B are exploded views and perspective views of the cap and fluid dispenser according to Figure 1. [Figure 3A] Figures 3A, 3B, and 3C are cross-sectional views of the sterile closed assembly of Figure 1, showing the connection of a fluid dispenser and a cap and the transfer of fluid into them, according to one embodiment. [Figure 3B] Figures 3A, 3B, and 3C are cross-sectional views of the sterile closed assembly of Figure 1, showing the connection of a fluid dispenser and a cap and the transfer of fluid into them, according to one embodiment. [Figure 3C] Figures 3A, 3B, and 3C are cross-sectional views of the sterile closed assembly of Figure 1, showing the connection of a fluid dispenser and a cap and the transfer of fluid into them, according to one embodiment. [Figure 3D] Figures 3D to 3E are cross-sectional views of the sterile closed assembly of Figure 1, showing the disconnection of the fluid dispenser and cap according to one embodiment. [Figure 3E] Figures 3D to 3E are cross-sectional views of the sterile closed assembly of Figure 1, showing the disconnection of the fluid dispenser and cap according to one embodiment. [Figure 4A] Figures 4A and 4B are cross-sectional views of a sterile closed assembly according to one embodiment, showing the connection between the fluid dispenser and the insert. [Figure 4B] Figures 4A and 4B are cross-sectional views of a sterile closed assembly according to one embodiment, showing the connection between the fluid dispenser and the insert. [Figure 5A] Figures 5A and 5B are perspective and cross-sectional views of a sterile closed assembly according to another embodiment. [Figure 5B] Figures 5A and 5B are perspective and cross-sectional views of a sterile closed assembly according to another embodiment. [Figure 6A] Figures 6A, 6B, and 6C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, according to one embodiment. [Figure 6B] Figures 6A, 6B, and 6C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, according to one embodiment. [Figure 6C]Figures 6A, 6B, and 6C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, according to one embodiment. [Figure 7A] Figures 7A, 7B, and 7C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, respectively, according to another embodiment. [Figure 7B] Figures 7A, 7B, and 7C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, respectively, according to another embodiment. [Figure 7C] Figures 7A, 7B, and 7C are perspective views, exploded views, and cross-sectional views of the cap of the sterile closure assembly shown in Figures 5A and 5B, respectively, according to another embodiment. [Figure 8A] Figures 8A and 8B are perspective and cross-sectional views of the sterile closed assembly shown in Figures 5A and 5B, respectively, illustrating the connection between the fluid dispenser and the cap according to one embodiment. [Figure 8B] Figures 8A and 8B are perspective and cross-sectional views of the sterile closed assembly shown in Figures 5A and 5B, respectively, illustrating the connection between the fluid dispenser and the cap according to one embodiment. [Figure 8C] Figures 8C and 8D are perspective views of the sterile closed assembly shown in Figures 5A and 5B, with a fluid container, according to one embodiment. [Figure 8D] Figures 8C and 8D are perspective views of the sterile closed assembly shown in Figures 5A and 5B, with a fluid container, according to one embodiment. [Figure 9A] Figures 9A and 9B are cross-sectional views of the sub-body and second port of a sterile closed assembly according to one embodiment. [Figure 9B] Figures 9A and 9B are cross-sectional views of the sub-body and second port of a sterile closed assembly according to one embodiment. [Figure 10A] Figures 10A and 10B are cross-sectional views of the sub-body and second port of a sterile closed assembly according to another embodiment. [Figure 10B] Figures 10A and 10B are cross-sectional views of the sub-body and second port of a sterile closed assembly according to another embodiment. [Figure 11A]FIG. 11A and FIG. 11B are perspective views of the sub-body and the second port of the sterile closure assembly according to the embodiments of FIGS. 10A to 10B. [Figure 11B] FIG. 11A and FIG. 11B are perspective views of the sub-body and the second port of the sterile closure assembly according to the embodiments of FIGS. 10A to 10B.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Like numerals represent like features.

[0011] The present disclosure generally relates to a sterile closure assembly for aseptically transferring 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 aseptically perform the coupling with a storage container and the transfer of fluid to and from the storage container, such as filling and removal, in order to avoid contamination. As used herein, the term "sterile" at least relates to forming a barrier or fluid path that remains intact between the fluid dispensing assembly and the fluid container in order 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. Although fluids related to chemical and / or biological processes are considered below, such consideration is not intended to limit the scope of the present invention and is understood to be provided as an embodiment of the present invention. Fluids include, but are not limited to, substances that flow or deform when a shear stress is applied. Fluids can include, for example, liquids.

[0012] For example, in the bioprocess market, customers freeze, transport, and thaw their drug products in various fluid storage containers such as bottles, bags, pails, and drums. While customers can aseptically transfer fluids to bag assemblies using various sterile connectors, the use of bottles, pails, drums, or larger bag assemblies is not as widespread. This is because the transfer of fluids to and from these bottles, pails, drums, or larger bag assemblies cannot be done using simple sterile connection assemblies. For example, since the fluid transfer assembly is connected to the top of the bottle, pail, drum, or larger bag assembly, the fluid transfer does not occur within a closed system, and additional equipment or mechanisms are required to maintain the sterility of the fluid. For example, customers may use bottles fitted with caps that have a pipe connection port on their top opening or a polymer stopper that covers the top opening of the bottle. Caps can be used to aseptically fill bottles, and polymer stoppers can be used to seal bottles; however, in either case, customers need to remove the caps and replace them with sturdy caps for freezing, transporting, and thawing process steps, or remove the polymer stoppers and fill and / or remove fluids, such as drug products. However, replacing bottle caps and / or polymer stoppers opens the system, exposing the fluid inside the bottle to the external environment, which can lead to potential fluid contamination. To limit and / or reduce the amount of contaminants that may enter the bottle during replacement of bottle caps and / or polymer stoppers, a hood can be used to attempt to maintain the sterility of the system. A system is needed for aseptically transferring fluids from fluid storage containers such as bottles, pails, and drums to simplify the filling and removal of fluids into bottles, for example, without requiring the use of hoods or additional equipment to maintain the sterility of the system, and to reduce the possibility of contaminating the fluid inside the bottle.

[0013] Embodiments of the present disclosure are directed toward a sterile closed assembly comprising a cap and a fluid dispenser that enables sterile transfer of fluid from a fluid container, such as a bottle having a rigid opening or other fluid container, such as a pail, bucket, or larger bag assembly having a rigid opening that can be fitted to the cap. It is understood that the rigid openings used herein are directed toward at least an opening formed in the fluid container of a relatively rigid material, such as one or more polymers. For example, fluid containers can be made from polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polycyclohexylenedimethylene terephthalate (PCTA), polycyclohexylenedimethylene terephthalate glycol (PCTG), polycarbonate (PC), polypropylene (PP), portamide (PA), polyethersulfone (PES), polyphenylsulfone (PPSU), polymethyl methacrylate (PMMA), high-impact polystyrene (HIPS), polyethylene naphthalate (PEN), polyetheretherketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, fluoropolymers, and copolymers containing these materials.

[0014] The sterile cap and fluid dispenser may include a versatile sterile cap that allows the user to sterilely connect and disconnect to a rigid opening in a body storage container, such as a bottle or bag assembly, before and after the freeze / thaw process step. The sterile closed assembly allows the user to fill the bottle before freezing and discharge it after thawing without the need to replace the cap and / or polymer stopper during the filling and discharging process, thus avoiding disruption 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, for example, fluid contamination by exposure to the external environment, and maintaining the sterility of the fluid in fluid handling systems, particularly those for bioprocess fluid handling. It is understood that, at least due to this design and structure of the aseptic sealed assembly, the fluid storage container and aseptic sealed assembly can be used in freeze / thaw process steps for applications as low as -85°C, and currently there are no existing aseptic cap designs that are considered suitable for use under such conditions, and especially for use in devices that perform dispensing and removal at such a top. Although the description of the fluid storage container and aseptic sealed assembly has been considered in relation to temperatures as low as -85°C, it is understood that the fluid storage container and aseptic sealed assembly can also be used at cryogenic temperatures lower than, for example, -190°C, and more preferably lower than -196°C.

[0015] Figure 1 is a schematic diagram of a sterile sealed assembly 10 for a fluid container 1 according to one embodiment. The sterile sealed assembly 10 may include a cap 12 connectable to the top opening of the fluid container 1 and a fluid dispenser 14, the cap 12 and the fluid dispenser 14 being configured to form a sealed fluid connection when joined together. The fluid dispenser 14 includes a fluid passage extending from the opening through the fluid dispenser 14. The cap 12 is configured to provide sterile fluid communication by sterile connecting the fluid passage of the fluid dispenser 14 to the fluid container 1 when the fluid dispenser 14 is connected to the cap 12, as will be discussed further below.

[0016] Thus, the sterile closure assembly 10 is configured to connect and disconnect sterilely 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 understood that the sterile closure assembly 10 can also be used at other temperatures, such as 0°C or room temperature, while maintaining the advantages of the present disclosure. Therefore, a fluid container 1 having the sterile closure assembly 10 as discussed above is configured to be stored at freezing temperatures (e.g., below 0°C). In one embodiment, the fluid container 1 having the sterile closure assembly 10 can also be heated back to ambient temperature without any substantial deformation. Substantial deformation includes, for example, visible cracking of the material, shrinkage or expansion of its original shape at ambient temperature, which may buffer the connection or adversely affect the sealing of the connection. Low-temperature elastic recovery tests can be performed according to ASTM D1329, ISO 2921, or any other suitable test method for determining appropriate shrinkage characteristics of the material at the temperatures at which it may be used. Brittleness testing can be performed according to ASTM D2137, ISO 28702, or any other suitable test method for determining the crack resistance of a material at the temperatures at which it may be used.

[0017] Fluid container 1 can generally be used to contain fluids suitable for use in manufacturing processes and / or biological processes, such as, but not limited to, semiconductor manufacturing, pharmaceutical manufacturing, or biological processing. In this case, it is understood that fluid container 1 can store liquid chemicals, including, but not limited to, photoresists, acids, solvents, bases, dopants, inorganic solutions, organic solutions, pharmaceuticals, and biological fluids.

[0018] In one embodiment, the fluid container 1 is a plastic bottle and / or may be a bag-in-bottle or bag-in-can type container. In other embodiments, the fluid container 1 may be a bag assembly having a rigid connecting structure such as a boat fitment, fitting, plastic port, and the like, or a combination thereof. It is understood that the container may be any type of container having a rigid opening 2 for attaching a sterile closed assembly 10, as will be discussed below. Such a fluid container 1 (or rigid connecting structure) may be made from a relatively rigid material, for example, one or more polymers. For example, the fluid container 1 may be made from polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polycyclohexylenedimethylene terephthalate (PCTA), polycyclohexylenedimethylene terephthalate glycol (PCTG), polycarbonate (PC), polypropylene (PP), portamide (PA), polyethersulfone (PES), polyphenylsulfone (PPSU), polymethyl methacrylate (PMMA), high-impact polystyrene (HIPS), polyethylene naphthalate (PEN), polyetheretherketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, and copolymers containing these materials.

[0019] The cap 12 is connectable to a 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 press-fitting the cap 12 into the rigid opening, or the cap 12 and the rigid opening 2 may include threaded portions that engage with each other. It is understood that the cap 12 may also be connected to the fluid container 1 in other ways, for example, by mechanical fasteners such as clamps and corresponding engagement mechanisms, or by welding or joining techniques such as thermal bonding, impulse welding, laser welding, ultrasonic welding, or similar fusion / melt welding techniques. In one embodiment, the cap 12 can be connected to the fluid container using a tamper-evident connection system. For example, a cap 12 having a tamper-evident connection system may include an inwardly biased retaining arm that, once pressed to a predetermined position on the rigid opening 2, engages with a corresponding projection around the rigid opening 2 of the fluid container 1, making it impossible to easily remove the cap 12 from the fluid container 1 without leaving any visible signs of damage to the cap 12 and / or the fluid container 1. In another embodiment, a cap 12 having a tamper-evident connection system may include a projection at the bottom of the threaded portion so that once the cap 12 is screwed to a predetermined position, it 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 may 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 warn the 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 possibly contaminated and / or damaged.

[0020] Figures 2A and 2B show embodiments of the aseptically sealed assembly 10 as described above. As seen in Figure 2A, the aseptically sealed 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 provided within the body between the first end and the second end, a shell housing 215 provided around the body 205, a set of seals 220, and an insert 225 that can be connected to and / or released from the second end of the body 205. The insert 225 can be connected to and / or released from the second end of the body by press-fitting it into the seal 220 provided around the second end of the body 205, for example. It is understood that the insert 225 can also be connected to the body 205 using various structures that enable the connection and release of the insert 225. For example, in one embodiment, the second end of the body 205 may include an engaging portion or projection extending from the second end of the body 205 that engages with a corresponding recess provided in the insert 225. In this case, the engaging portion or projection of the second end of the body 205 can be inserted into and rotated within the recess of the insert 225 for connecting and disconnecting the insert 225 from the body 205.

[0021] The fluid line 210 may include a tube connector near the first end of the main body 205 for connecting to a fluid transfer system for transferring fluid to the fluid container 1, for example, filling or removing it. The tube connector can be selected from the group consisting of hose barbs, overmolded connectors, threaded connectors, press-fit connectors, snap-fit ​​connectors, or a combination thereof. It is also understood that the tube connector may be formed in conjunction with the fluid transfer system, for example, by molding or overmolding the fluid dispenser 14 together with the fluid transfer system.

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

[0023] As shown in Figure 2B, the cap 12 includes a housing 240, a cavity 245 within the housing 240, a support portion 250 provided in the cavity 245, and a set of seals 255. The housing 240 of the cap 12 includes a second retaining mechanism 260 having a shape complementary to the first retaining mechanism 235, which allows for the engagement of a first retaining mechanism 235 with a second retaining mechanism 260 so that the fluid dispenser 14 is securely attached to the cap 12, and for the engagement and disengagement of the second retaining mechanism 260 so that the fluid dispenser 14 is released from the cap 12. It is understood that the first retaining mechanism 235 may include a plurality of arms having hooks that connect to the corresponding second retaining mechanism 260, for example, that snap, slide, or fit into the inside or outside of the second retaining mechanism 260. It is also understood that the first retaining mechanism 235 and the second retaining mechanism 260 may include other structures for engaging and disengaging the fluid dispenser, for example, the second retaining mechanism 260 may include a plurality of slots or threads that enable engagement and rotation of the first retaining mechanism 235 to ensure attachment of the fluid dispenser 14 to the cap 12, or may include slots, tabs, flanges, retainers, hooks, or any other suitable structure for holding the first retaining mechanism 235. The seal set 255 may include a first seal 255 located around 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 located around 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 portion 250 are provided 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 the fluid is transferred into the fluid container 1, the insert 225 is inserted into the support portion 250 of the cavity 245 by at least a downward force toward the fluid container 1, thereby disconnecting the insert 225 from the body 205 of the fluid dispenser 14 and sealing the fluid container, for example, the insert 225 is press-fitted into the cap 12 without requiring additional equipment or replacement of the cap 12. It is understood that the insert 225 may also seal the cap 12 using other structures for engaging / disengaging the insert 225, such as a screw connection system, engaging portions and recesses, raised portions or protrusions.

[0025] The sterile closed assembly 10, including the fluid dispenser 14 and the cap 12, may be fabricated from the same or similar materials as the fluid container 1 and / or each other, or from a combination thereof. In one embodiment, the fluid dispenser 14, including the body 205, the shell housing 215, and the insert 225, and the cap 12, may be fabricated from polyolefins, such as, but not limited to, polypropylene, high-density polyethylene, or linear low-density polyethylene. Other non-limiting examples of polymers suitable for fabricating various embodiments of the sterile closed assembly 10, including the cap 12 and the fluid dispenser 14, include fluoropolymers, polyesters, polycarbonates, and polyamides. It will be understood 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 this disclosure, not limited to the list provided, 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 may differ from the material of the fluid dispenser 14. In another embodiment, the various components of the fluid dispenser 14, such as the body 205, shell housing 215, and insert 225, may be made of the same material, different materials, or a combination thereof.

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

[0027] The operation of the sterile closed assembly 10 with the fluid dispenser 14, and its connection / disconnection to the cap 12, will be discussed below with reference to Figures 3A to 3E. It is understood that the sterile closed assembly 10 can be used for the transfer of fluid to and from a fluid container, which may be either filling or removing fluid. For example, if the sterile closed assembly 10 is used to fill a fluid container, one of the fluid lines is used to evacuate any gas in the fluid container, and the gas is replaced as the fluid fills the fluid container. Alternatively, if the sterile closed assembly 10 is used to remove fluid from a fluid container, one of the fluid lines can be used to supply an inert gas, such as nitrogen or air, to induce a fluid flow 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 for filling a fluid container will be discussed below.

[0028] Figures 3A to 3C show a fluid dispenser 14 connected to a cap 12 for transferring fluid, such as a packing, into a fluid container 1, where the cap 12 is connected to and fixed to a rigid opening 2 of the fluid container 1. The fluid dispenser 14 is fixed to the cap 12 via a holding mechanism (not shown) for the fluid dispenser 14 and the cap 12. As discussed above, initially, the opening 206 of the body 205 is sealed to the shell housing 215 by the seals 220 together, for example, between the first seal and the second seal, so that fluid cannot be dispensed from the fluid dispenser 14. When the fluid dispenser 14 is connected to the cap 12 and ready to transfer fluid, the body 205 is pushed downward toward the fluid container 1 so that the opening 206 of the body 205 is in fluid communication with the enlarged portion 230 of the shell housing 215. In this way, as seen in Figures 3B and 3C, the second seal 220 is placed within the enlarged portion, and as a result, as indicated by arrow F, the fluid can be transferred 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 portion 250, and into the fluid container 1. The fluid dispenser 14 may include a second fluid line 210, which is understood to be usable for the transfer of fluid and / or as an exhaust port that takes a path opposite to the fluid filling, allowing the fluid container 1 to be evacuated when the fluid replaces the gas inside the fluid container 1.

[0029] As shown in Figures 3D to 3E, after the transfer of fluid into the fluid container 1 is complete, the fluid dispenser 14 can be guided further downward toward the fluid container 1 so that the insert 225 fits into the support portion 250 of the cavity 245. When the insert 225 is inserted into the cavity 245, the fluid container 1 is sealed by the seal 255 that engages with the insert 225 at the opening of the cavity 245. As shown in Figure 3E, the engagement force of the insert 225 into the cavity 245 is greater than the engagement force of the insert 225 to the second end of the body 205, for example, due to the compressibility and / or elastic modulus of the seal. Therefore, when the fluid dispenser 14 is disengaged from the cap 12, the insert 225 is disengaged from the second end of the body 205 and remains inserted in the cavity 245, sealing the fluid container 1 when the fluid dispenser 14 is disengaged from the cap 12. It is understood that the fluid dispenser 14 may be configured such that when the seal 220 is pushed downward, the opening 206 can be sealed by sealing the second end of the body with the shell housing 215, or the body 205 may be moved upward, as a result the opening 206 will detach from the enlarged portion 230 and be sealed between the first and second seals 220 and the shell housing 215. It is also understood that the insert 225 may be engaged with the cavity 245 and / or support portion 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 retaining mechanism such as a hook or projection or screw connection that engages with the insert 225 by engaging with a complementary retaining mechanism of the cavity 245 and / or support portion 250, and detaches the insert 225 from the body 205. In another embodiment, the insert 225 may include a permanent retention mechanism, for example, a hook structure that, when inserted into the cavity, is biased outward to engage with complementary structures of the cavity 240 and / or support 250. In such a case, since the insert is permanently fixed to the cap 12, the sterile closed assembly cannot be used for multipurpose applications.

[0030] In another embodiment, as seen in Figures 4A and 4B, the aseptic closure assembly 10 includes an insert 425 that is removable from the cavity 240 and / or support portion 250 of the cap 12. The aseptic closure assembly 10 of Figures 4A and 4B has the same or similar features as the aseptic 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 engaging piece 407, such as a hook piece, for engaging with a complementary engaging piece or engaging member 426 of the insert 425. In one embodiment, the complementary engaging piece or member 426 of the insert 425 may include an opening that allows the engaging piece 407 of the body 205 to be inserted below the engaging piece or member 426 so that the engaging piece 407 of the body 205 engages with the complementary engaging piece or member 426 of the insert 425 as the body 205 of the fluid dispenser 14 rotates. In this case, as shown in Figure 4B, when the insert 425 is inserted into the cap 12 of the fluid container 1 and sealing it, if an upward force is applied to the body 205 of the fluid dispenser 14, the engaging piece 407 of the body 205 engages with the complementary engaging piece or member 426 of the insert 425, and as a result the insert 425 becomes removable from the cavity 245 and / or support 250, and as a result the fluid can be transferred to, for example, filled or removed from, the fluid container 1. After the fluid transfer by the fluid container 1 is complete, the insert 425 can be removed, or, as shown in Figure 4A, the body 205 of the fluid dispenser 14 can be guided downward toward the fluid container 1 (as discussed above with respect to Figures 2A and 2B), and the body 205 can be rotated so that the insert 425 is disengaged from the body 205 by removing the engaging piece 407 of the body 205 through the opening of the insert 425, thereby fitting the insert 425 into the support portion 250 of the cavity 245. Once the insert 425 is inserted into the cavity 245, the fluid container 1 is sealed by the insert 425 and seal 255 sealing the opening of the cavity 245.In one embodiment, it is understood that the seal 220 on the second end of the body 205 prevents contamination of any contents on the top surface of the insert 425 by sealing the body 205 against the insert 425 during fluid transfer. Also in one embodiment, it is understood that a film, cap, valve, or similar sealing device that maintains a tight seal can be attached to and / or coupled to the cap 12 of the fluid container and / or the fluid dispenser 14 for sterile connection / disconnection of the fluid container. The film, cap, valve, or similar sealing device can then be punctured, removed, and / or rotated to allow transfer of sterile fluid when the fluid container is coupled to the fluid dispenser 14.

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

[0032] Thus, the sterile closure assembly 502 is configured to connect to and disconnect from a fluid container for sterile transfer of fluids within a fluid container usable at temperatures as low as -85°C. It is understood that the sterile closure assembly 502 can also be used at other temperatures, such as 0°C or room temperature, while maintaining the advantages of the present disclosure. Therefore, a fluid container having the sterile closure assembly 502 as discussed above is configured to be stored at freezing temperatures (e.g., below 0°C). In one embodiment, a fluid container having the sterile closure assembly 502 can also be heated back to ambient temperature without any substantial deformation. Substantial deformation includes, for example, visible cracking of the material, shrinkage or expansion of its original shape at ambient temperature, which may clash with the connection or adversely affect the sealing of the connection. Low-temperature elastic recovery tests can be performed according to ASTM D1329, ISO 2921, or any other suitable test method for determining appropriate shrinkage characteristics of the material at the temperatures at which it may be used. Brittleness testing can be performed according to ASTM D2137, ISO 28702, or any other suitable test method for determining the crack resistance of a material at the temperatures at which it 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 press-fitting the cap 512 into the rigid opening, or the cap 512 and the rigid opening may include threaded portions that engage with each other. It is understood that the cap 512 may also be connected to the fluid container 1 in other ways, for example, by mechanical fasteners, such as clamps, corresponding engagement mechanisms, or by welding or joining techniques, such as thermal bonding, impulse welding, laser welding, ultrasonic welding, or similar fusion / melt welding techniques. In one embodiment, the cap 512 can be connected to the fluid container using a tamper-evident connection system. For example, a cap 512 having a tamper-evident connection system may include an inwardly biased retaining arm that engages with a corresponding projection around a rigid opening of the fluid container, and once the retaining arm is pushed to a predetermined position on the rigid opening, it becomes impossible to easily remove the cap 512 from the fluid container without leaving any visible signs of damage to the cap 512 and / or the fluid container. In another embodiment, a cap 512 having a tamper-evident connection system may include a projection at the bottom of the threaded portion, so that once the cap 512 is screwed to a predetermined position, it 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 may 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 the customer or user of the fluid container having the cap 512 if the fluid container has been opened or attempted to be opened, and possibly 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 retaining mechanism 560 having a shape complementary to a first retaining mechanism 535 on the body 505 and sub-body 508 of the fluid dispenser 514 for engaging with the outer surface of the housing 540 of the cap 512. The first retaining mechanism 535 can engage with the second retaining mechanism 560 to securely attach the fluid dispenser 514 to the cap 512 and can engage and disengage to remove the fluid dispenser 514 from the cap 512. For example, in one embodiment, the second retaining mechanism 560 may include a pin or projection that engages with a corresponding slot formed by the first retaining mechanism 535 on the body 505 and sub-body 508 of the fluid dispenser 514. Insert 525 is configured to be engageable and disengaged with port 570 so as to open and close a fluid communication channel between the fluid container and port 570, as will be further discussed below. For example, in one embodiment, the fluid dispenser 514 is configured such that the cap 512 engages with insert 525 after it has been connected to the fluid container, thereby connecting the insert 525 onto the fluid dispenser 514 due to a downward force toward the fluid container and its rotation, and allowing the insert 525 to be disengaged from port 570 so that the body 505 (and / or sub-body 508) of the fluid dispenser 514 can be inserted into the fluid container for sterile transfer of fluid to and from the fluid container. It is understood that after the fluid has been transferred to the fluid container, the insert 525 can be re-engaged with port 570 so as to seal port 570 and seal 555 so as to prevent fluid communication between port 570 and the fluid container.

[0035] For example, in one embodiment, as seen in Figures 6A, 6B, and 6C, the cap 512 includes a housing 540, a cavity 545 within the housing 540, a port 570 connected to the cavity, and a set of seals 555. Each port 570 includes a port shell 571 and an insert 525 connected to one end of the port shell 571. The insert 525 is configured to be engageable and disengageable with the port shell 571 so as to open and close a fluid communication channel between the fluid vessel and the port 570, as will be further discussed below. For example, in one embodiment, the insert 525 includes an outer engaging piece or member 527 spaced along the periphery of the insert 525, which is engageable with a complementary outer engaging piece or member 572 provided on the outer surface of the port shell 571. In one embodiment, a space is provided between an outer engaging piece or member 527 and a complementary engaging piece or member 572, and the insert 525 can be engaged with and disengaged from the port shell 571 by rotating the insert 525 so that it is positioned within the corresponding space. When the insert 525 is engaged with the port shell 571, it is understood that a seal 555 provided along the inner circumference of the outer engaging piece or member 527 seals the port 570 so that it does not come into fluid communication with the fluid container. It is understood that the port 570 may have the same or similar structure, or may have a different structure, as will be 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. Each port 770 includes 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 so as to open and close a fluid communication channel between the fluid vessel and the port 770, as will be further discussed below. For example, in one embodiment, the insert 725 includes an outer engaging piece or member 727 spaced along the circumference of the insert 725, which is engageable with a complementary outer engaging piece or member 772 provided along the inner circumference of the port shell 771. In one embodiment, a space is provided between an outer engaging piece or member 727 and a complementary engaging piece or member 772, allowing the insert 725 to engage with and disengage from the port shell 771 by rotating the insert 725 so that it is positioned within the corresponding space. Once the insert 725 is engaged with the port shell 771, it is understood that a seal 720 provided along the outer circumference of the insert 725 seals the port 770 so that it does not come into fluid communication with the fluid container. While the inserts 525, 725 and the port shells 571, 771 have been considered above as having an outer engaging piece and a complementary engaging piece or member, it is understood that such disclosures are intended to be non-limiting disclosures, including other mechanical structures that enable the insert to be engageable with and disengaged from the port. For example, screw connections or snap fits may be used to engage and disengage the insert from the port.

[0037] Although the cap 512 is illustrated and shown as a separate part, it is understood that such disclosure is not intended to be limiting. For example, the cap 512 may be constructed from a port connected to the housing, or the cap 512 may be constructed as a single molded part or component. In that case, various inserts may be used to complement the engaging piece of the fluid dispenser. The port 570 may be a single port provided on the cap 512, in which case it is understood that the port 570 is configured to allow connection to two separate fluid lines of the fluid dispenser to which it is connected.

[0038] Referring again to Figures 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 provided around the body 505, a sub-housing 509 provided around 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, which is fluidly connected to the fluid line 510 and configured to be in fluid communication with the 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 retaining mechanism 535 for engaging with the outer surface of the housing 540 of the cap 512, as discussed above. The shell housing 515 includes a foldable structure to allow the fluid line 510 to be inserted into a fluid container while maintaining the sterility of the fluid line 510. For example, in one embodiment, the shell housing 515 includes an accordion-like structure having a bellows section that folds and expands to allow compression and expansion of the shell housing 515 when the fluid line 510 moves in and out of the shell housing 515, such as when the fluid line 510 is used as an immersion tube inserted into a fluid container. It is understood that other foldable structures may be used, such as a sealed sliding shell within the shell housing, or a similar structure that allows sterile fluid communication with a fluid container. The sub-body 508 may have the same or similar structure as the main body 505, and in one embodiment, the sub-body 508 includes a sub-shell housing 509 around the sub-body 508 that only partially allows the movement of the fluid line 510 into the fluid container by the rotation of the sub-body 508, for example, not having a structure as an immersion tube and only allowing partial insertion into the fluid container.

[0039] The fluid line 510 may include a tube connector near the first end of the main body 505 and the sub-body 508 for connecting to a fluid transfer system for transferring fluid to a fluid container, for example, filling or removing it. The tube connector can be selected from the group consisting of hose barbs, overmolded connectors, threaded connectors, press-fit connectors, snap-fit ​​connectors, or a combination thereof. It is also understood that the tube connector may be formed in conjunction with the fluid transfer system, for example, by molding or overmolding the fluid dispenser together with the fluid transfer system.

[0040] In one embodiment, a fluid dispenser 514 including a main body 505 and a sub-body 508 includes a projection on the engaging piece 507 having a shape that aligns with complementary engaging members 526, 726 (as shown in Figures 6B and 7B) of inserts 525, 725 located on the second ends of the main body 505 and the sub-body 508. For example, the engaging members 526, 726 include an opening that can receive the engaging piece 507 of the main body 505 and / or sub-body 508 so that the engaging piece 507 of the main body 505 and / or sub-body 508 engages with the complementary engaging piece or member 526, 726 of inserts 525, 725 as the main body 505 and / or sub-body 508 rotates. In response, when a downward rotational force is applied to the main body 505 and / or sub-body 508 of the fluid dispenser 514, the engaging pieces 507 of the main body 505 and / or sub-body 508 engage with the complementary engaging members 526 and 726 of the inserts 525 and 725, and as a result, further rotation of the main body 505 and / or sub-body 508 causes the inserts 525 and 725 to rotate, engaging and disengaging them from the port 570. The inserts 525 and 725 are then inserted into the fluid container, and as a result, fluid can be transferred from the fluid container, for example, to fill or remove it. After the transfer of fluid by the fluid container is complete, the inserts 525 and 725 can be guided upward toward the port 570 so that they can be rotated to engage with the port 570 and seal it. When inserts 525, 725 are inserted into the cavity 545 and port 570, the fluid container is sealed by the inserts 525, 725 and seal 555 sealing port 570. In one embodiment, it is also understood that a film, cap, valve, or similar sealing device that maintains a tight seal can be attached to and / or coupled to the cap 512 and / or port 570 and / or fluid dispenser 514 of the fluid container for sterile connection / disconnection of the fluid container. The film, cap, valve, or similar sealing device can then be punctured, removed, and / or rotated to allow further transfer of sterile fluid when the fluid dispenser 514 is coupled to the fluid container.

[0041] The sterile closed assembly 502, comprising the fluid dispenser 514 and the cap 512, may be fabricated from the same or similar materials as the container and / or each other, or from a combination thereof. In one embodiment, the fluid dispenser 514, comprising the main 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 fabricated from polyolefins, such as, but not limited to, polypropylene, high-density polyethylene, or linear low-density polyethylene. Other non-limiting examples of polymers suitable for fabricating various embodiments of the sterile closed assembly 502 comprising the cap 512 and the fluid dispenser 514 include fluoropolymers, polyesters, polycarbonates, and polyamides. It will be understood that these materials are examples, and that the actual materials of the cap 512 and the fluid dispenser 514 may vary within the principles of this disclosure, not limited to the list provided, or may be a mixture of any of the above. 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 may be different from the material of the fluid dispenser 514. In another embodiment, the various components of the fluid dispenser 514, such as the main body 505, sub-body 508, shell housing 515, sub-shell housing 509, and insert 525, may be made of the same material, different materials, or a combination thereof. In one embodiment, the shell housing 515 may be made of silicon or a flexible polymer so as 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 a combination thereof, of silicone, fluoropolymer, ethylene vinyl acetate (EVA), thermoplastic materials, or other flexible and / or compressible biocompatible sealing materials that are relatively inert, do not filter or significantly absorb pharmaceutical or biological fluids, and are non-reactive. Other seals may also be quad rings, or thermoplastic or other flexible and / or compressible sealing materials formed from any of the above materials, which are melt-formed, e.g., overmolded or insert-molded, to fill grooves in corresponding members with the thermoplastic or flexible material.

[0043] The operation of the fluid dispenser 514 and its connection / disconnection to the cap 512 will be examined below with reference to Figures 8A to 9C. Any of the inserts, ports, and related structures discussed above can be used, but it is understood that the following discussion will focus on insert 525 as a non-limiting example.

[0044] Figures 8A and 8B show the body 505 of a fluid dispenser 514 connected to a cap 512 for transferring fluid, such as a packing, into a fluid container, where the cap 512 is connected to and secured to the rigid opening of the fluid container. The body 505 of the fluid dispenser 514 is secured to the cap 512 by rotating the first retaining mechanism 535 of the fluid dispenser 514 onto the second retaining mechanism 560 on the port 570 of the cap 512. Initially, the opening 506 of the body 505 is sealed to the shell housing 515 by seals 520 together, for example, between the first seal and the second seal, to prevent fluid from being dispensed from the body 505 of the fluid dispenser 514. When the body 505 of the fluid dispenser 514 is connected to the cap 512 and ready to transfer fluid, the body 505 is pushed downward toward the fluid container and rotated so that the engaging piece 507 on the body 505 engages with the complementary engaging 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 engaging piece 527 disengages from the complementary engaging 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, forming a sterile fluid communication channel between the fluid dispenser 514 and the fluid container.

[0045] For example, as shown in Figures 8C and 8D, the fluid line 510 and insert 525 can be directed downward toward the fluid container 501 such that the opening 506 is no longer positioned 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 as immersion tubes that can be lowered (or raised) near the fluid level for the transfer of fluid into and from the fluid container 501, for example, to prevent foaming or to allow fluid discharge. In one embodiment, when the opening 506 and insert 525 are displaced toward the fluid container 501, the shell housing (e.g., a 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 kept sterile, as it only comes into contact with the inner surface of the shell housing and the fluid in the fluid container 501. Furthermore, since the fluid line 510 can be lowered (or raised) at different heights, it is understood that such a structure enables the automatic filling or removal of fluid from the fluid container 501. For example, the shell housing and / or fluid line (if the shell housing is transparent) may include indicator marks or measurements to show 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 process is complete, the opening 506 and insert 525 can be raised upward so that the opening 506 is positioned between the seal 520 and the shell housing 515, and the insert 525 is rotated to engage with the port 570. Once the insert 525 is engaged with the port shell 570, it is understood that the seal 555, provided along the inner circumference of the outer engaging piece or member 527, seals the port 570 so that it does not come into fluid communication with the fluid container 501. Further rotation of the body 505 causes the engaging piece 507 on the body 505 to engage and disengage with the complementary engaging member 526 of the insert 525. Thus, by rotating the fluid dispenser 514 so that the first retaining mechanism 535 of the body 505 of the fluid dispenser engages and disengages with the second retaining mechanism 560 on the port 570 of the cap 512, the fluid dispenser 514 can be removed from the cap 512 and the fluid container 501. Since the insert 525 is only in contact with the fluid dispenser 514 for the transfer of fluid to and from the fluid container 501, it is understood that the fluid processing system remains closed, as there is no need for secondary steps to seal the fluid container 501, such as replacing the sterile closure assembly and stopper which would make the fluid processing system susceptible to contamination.

[0047] Similarly, as shown in Figure 8D, the sub-body 508 of the fluid dispenser 514 can be connected to the cap 512 by rotating the first holding mechanism 535 onto the second holding mechanism 560 on the port 570 of the cap 512. For example, as shown in Figures 9A to 9B, initially the opening 506 of the sub-body 508 is sealed to the sub-shell housing 509 between the seals 520, for example, the first seal and the second seal, and therefore fluid cannot be transferred through the sub-body 508 of the fluid dispenser 514. When the fluid dispenser 514 is connected to the cap 512 and ready to transfer fluid, the sub-body 508 can be pushed downward toward the fluid container 501 and rotated so that the engaging piece 507 on the sub-body 508 engages with the complementary engaging member 526 of the insert 525. After the sub-body 508 and the insert 525 engage, the sub-body 508 is further rotated so that the outer engaging piece 527 engages with and disengages from the complementary engaging 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, forming a fluid communication channel between the sub-body 508 of the fluid dispenser 514 and the fluid container.

[0048] For example, as shown in Figure 9B, the fluid line 510 and insert 525 can be directed downward toward the fluid container 501 such that the opening 506 is no longer located between the seal 520 and the sub-housing 509. The opening 506 and insert 525 can then be displaced within the fluid container 501 below the cap 512 for the transfer of fluid into and from the fluid container 501. In one embodiment, when the opening 506 and insert 525 are displaced toward the fluid container 501, the sub-shell housing 509 allows the fluid line 510 to be moved, at least partially, toward the fluid container 510 such that the sterility of the fluid is maintained without any part of the outer surface of the fluid line 510 being exposed to the environment.

[0049] After the fluid transfer process is complete, the opening 506 and insert 525 can be raised upward so that the opening 506 is positioned between the seal 520 and the sub-shell housing 509, and the insert 525 is rotated so that the insert 525 engages with the port 570. When the insert 525 engages with the port shell 570, it is understood that the seal 555, provided along the inner circumference of the outer engaging piece or member 527, seals the port 570 so that it does not fluidly communicate with the fluid container 501. Further rotation of the sub-body 508 causes the engaging piece 507 on the sub-body 508 to engage and disengage with the complementary engaging member 526 of the insert 525. Therefore, when the sub-body 508 of the fluid dispenser 514 is rotated, the first retaining mechanism 535 of the sub-housing shell 509 engages and disengages with the second retaining mechanism 560 on the cap 512, allowing the fluid dispenser 514 to be removed from the cap 512 and the fluid container 501. Since the insert 525 is only in contact with the fluid dispenser 514 for the transfer of fluid to and from the fluid container 501, it is understood that the fluid processing system remains closed, as there is no need for a secondary step to close the fluid container 501, such as replacing a sterile closure assembly and stopper that would make the fluid processing system susceptible to contamination.

[0050] Another embodiment of the sub-body and the second port is shown in Figures 10A to 10B. In this embodiment, the second port 1070 has a different structure from the first port (e.g., port 570 as discussed above), and the sub-body 1008 has a different structure from 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 to 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 provided to seal one end of the second port 1070, and a first spring 1080 that biases the second insert 1025 to a closed position, for example, an upward position away from the fluid container. The fluid dispenser includes a sub-body 1008 having a second shell housing 1009, a sealing end 1013 provided within the second shell housing 1009, a second spring 1011 that biases the sealing end 1013 within the second shell housing 1009 toward an opening 1006 of the sub-body 1008, and a third set of seals 1020. The second shell housing 1009 is configured to engage with the outer surface of a second port 1070, and the connection of the second shell housing 1009 to the second port 1070 causes the sub-body 1008 to bias the insert 1025 toward the fluid container, thereby providing a second fluid communication channel between the sub-body 1008 and the fluid container.

[0051] As shown in Figure 10A, initially, the opening 1006 of the sub-body 1008 is sealed to the sub-shell housing 1009 by a seal 1020, for example, between the first seal and the sealing end 1013, and therefore, fluid cannot be transferred through the sub-body 1008 of the fluid dispenser. When the sub-body 1008 of the fluid dispenser is connected to the cap 1012 and ready to transfer fluid, the sealing end 1013 is biased away from the second end of the sub-body 1008, opening the fluid communication channel of the opening 1006. The sub-body 1008 can also be pushed downward toward the fluid container and rotated so that the insert 1025 is biased toward the fluid container so that a fluid communication channel is formed between the opening 1006 of the sub-body 1008 of the fluid dispenser and the fluid container. For example, in one embodiment, a downward force toward the fluid container biases the sealing end 1013 against the second shell housing 1009 so that the opening 1006 can communicate fluidly with the port 1070. The second end of the sub-body 1008 engages with the insert 1025, thereby causing the insert 1025 to displace relative to the port 1070 so that a subsequent downward force can cause the fluid to flow around the insert 1025 into the fluid container.

[0052] After the fluid transfer process is complete, the opening 1006 and insert 1025 can be rotated so that the spring 1080 biases the insert 1025 to the closed position. The insert 1025 engages with the second port 1070 so that the seal 1055 and the insert 1025 seal the port 1070 so that there is no fluid communication with the fluid container. Further rotation of the sub-body 1008 disengages the second shell housing 1009 from the second port 1070, and the spring 1011 biases the sealing end 1013 toward the second end of the sub-body 1008 so that the opening 1006 is positioned between the seal 1020 and the sealing end 1013 of the sub-body 1008. Since the insert 1025 is only in contact with the sub-body 1008 of the fluid dispenser for the transfer of fluid to and from the fluid container, it is understood that the fluid processing system remains closed, as there is no need for a secondary step to close the fluid container, such as replacing the sterile closure assembly and stopper, which would make the fluid processing system susceptible to contamination.

[0053] In one embodiment, it is understood that the second port 1070 forms a fluid connection to a fluid container such that when the insert is pushed downward, a fluid communication channel with the fluid container is directly formed. In another embodiment, as shown in Figures 11A and 11B, the second port 1070 includes a pipe with an angled design, such as a J-pipe design, so that the fluid is directed to the side of the fluid container. The J-pipe can be press-fitted into the port or mechanically attached, for example, with screws, bolts, etc. The angled pipe design avoids foaming 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. Figures 11A and 11B further illustrate that ports 570 and 1070 may have different designs, such as a baffle design in which the main body 505 of the fluid dispenser 514 connects to the first port 570, and a sub-body 1008 of the fluid dispenser 514 connects to the second port 1070 for the transfer of fluid into the fluid container 501. It is understood that the cap ports may have the same or different designs depending on the application and are not limited to the designs discussed above.

[0054] In another embodiment, a method is provided for aseptically transferring fluid into or from a fluid container for freeze / thaw applications. Referring to Figures 5A and 5B, the method includes the step of connecting a cap 512 to the opening of a fluid container. The cap 512 includes a housing 540, a cavity 545 within the housing 540, a port 570 connected to the cavity 545, and a set of seals 555. The port 570 includes a port shell 571 and an insert 525 connected to one end of the port shell 571, the insert 525 being configured to open and close a fluid communication channel between the fluid container and the port 570. The method further includes transferring the fluid into the fluid container by aseptically connecting and disconnecting a fluid dispenser 514 to the 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 provided around the body 505, a second set of seals, a sub-shell housing 509 provided around the sub-body 508, and engaging pieces 507 on the body 505 and sub-body 508 that are engageable with an insert 525. When the engaging pieces 507 of the fluid dispenser engage with the insert 525 of the port 570 by rotational engagement, the fluid line 510 is guided downward toward the fluid container together with the insert 525, opening a fluid communication channel with the fluid container so that fluid can be transferred to, for example, filled or removed from the fluid container. After the transfer of fluid by the fluid container is complete, the insert 525 is guided upward toward the port 570 so that the insert 525 can be rotated to engage with the port 570 and seal it. When insert 525 is inserted into the cavity 545 and port 570, the fluid container is sealed by the insert 525 and seal 555 sealing port 570.

[0055] The fluid container can then be used during storage, transport, and manufacturing processes. For example, in one embodiment, the fluid container can be frozen so that the transferred fluid inside the 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 fluid flow. The fluid dispenser 514 can then be used for aseptic 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 so that the fluid line 510 is aseptically 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 of the body 508.

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

[0057] Embodiment 1 A sterile closed assembly for a fluid container, comprising: a cap connectable to the opening of a fluid container, comprising a housing, a cavity within the housing having a support, and a first set of seals; and a fluid dispenser connectable to the outer surface of the housing of the cap, comprising a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided around the body, a second set of seals, and an insert connectable to the second end of the body, wherein the body includes an opening near the second end, connected to the fluid line and configured to communicate with the fluid container when the fluid dispenser is connected to the cap, and the fluid dispenser is configured such that a downward force toward the fluid container causes the insert to engage with the support in the cavity, and the insert is disconnected from the body of the fluid dispenser to seal the fluid container.

[0058] Embodiment 2: The sterile sealed assembly according to Embodiment 1, wherein the fluid container is a bottle.

[0059] Embodiment 3 A sterile closed assembly according to any one of Embodiments 1 to 2, wherein the shell housing comprises an opening and an enlarged portion communicating with fluid, and when fluid is supplied or removed through the fluid line of a fluid dispenser, the fluid flows from the opening through the enlarged portion and around the insert into the fluid container, or from the fluid container through around the insert and the enlarged portion and then through the opening.

[0060] Embodiment 4: A sterile closed assembly according to any one of Embodiments 1 to 3, wherein the insert is disconnected from the main body by press-fitting 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] Embodiment 5 The sterile closure assembly according to Embodiment 4, wherein the first set of seals comprises a first seal around the outer surface of a cap connectable to the inner surface of a shell housing, and a second seal around a cavity.

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

[0063] Embodiment 7 A sterile closed assembly according to any one of Embodiments 1 to 6, wherein the shell housing comprises a plurality of first retaining mechanisms extending from one end of the shell housing, configured to engage with a second retaining mechanism provided on the outer surface of the housing of the cap, the first retaining mechanisms and the second retaining mechanisms having complementary shapes.

[0064] Embodiment 8: A sterile closure assembly according to any one of Embodiments 1 to 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] Embodiment 9 A sterile closed assembly according to any one of Embodiments 1 to 8, wherein at least one of the cap or insert comprises a fluoropolymer.

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

[0067] Embodiment 11 The sterile closed assembly according to Embodiment 4, wherein the fluid dispenser comprises an engaging piece for engaging with the insert, or an engaging member that allows the fluid dispenser to engage with the insert so that the insert can be removed from the support portion of the cavity by rotating the fluid dispenser.

[0068] Embodiment 12 A sterile closed assembly according to any one of Embodiments 1 to 11, comprising a plurality of arms extending from one end of the shell housing, configured to engage with a plurality of corresponding slots provided on the outer surface of the housing of the cap, wherein the plurality of arms and the plurality of slots have complementary shapes that enable them to engage and disengage.

[0069] Embodiment 13 A sterile closed assembly according to any one of Embodiments 1 to 11, further comprising means for engaging and disengaging a fluid dispenser and a cap.

[0070] Embodiment 14 A sterile closed assembly for a fluid container, comprising: a cap connectable to the opening of a fluid container, comprising a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals, wherein the port comprises a port shell and an insert connected to one end of the port shell, the insert being configured to open and close a fluid communication channel between the fluid container and the port; and a fluid dispenser connectable to the outer surface of the port shell, the fluid dispenser comprising a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided around the body, a second set of seals, and an engaging piece that can engage with the insert, the engaging piece of the fluid dispenser being able to engage with the insert of the port by rotational engagement so that the fluid line can be guided downward toward the fluid container together with the insert so that a fluid communication channel with the fluid container is opened.

[0071] Embodiment 15 A sterile closure assembly for a fluid container according to Embodiment 14, the cap comprising a second cavity and a second port connected to the second cavity, wherein the second port comprises a second shell, a second insert provided to seal one end of the second port, and a first spring that biases the second insert to a closed position.

[0072] Embodiment 16 A sterile closed assembly for a fluid container according to Embodiment 15, further comprising a sub-body of a fluid dispenser having a second shell housing, a second spring for biasing the sub-body within the second shell housing, and a third set of seals, wherein the second shell housing is configured to engage with the outer surface of a second port, and the connection of the second shell housing to the second port causes the sub-body to bias an insert toward a fluid container, thereby providing a second fluid communication channel between the sub-body and the fluid container.

[0073] Embodiment 17 The sterile closed assembly for a fluid container according to Embodiment 16, further comprising a pipe connected to the second port, the second port being configured to guide fluid to the side of the fluid container.

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

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

[0076] Embodiment 20 A method for aseptically transferring fluid into or from a fluid container, comprising the steps of connecting a cap to the opening of a fluid container, the cap comprising a first set of a housing, a cavity within the housing, a port connected to the cavity, and a seal, the port comprising a port shell and an insert connected to one end of the port shell, the insert being configured to open and close a fluid communication channel between the fluid container and the port, and connecting and disconnecting a fluid dispenser aseptically to the outer surface of the port shell A method comprising the step of transferring a fluid into a fluid container, wherein the fluid dispenser comprises a body having a first end and a second end, a fluid line provided within the body between the first end and the second end, a shell housing provided around the body, a second set of seals, and an engaging piece that can engage with an insert, and when the engaging piece of the fluid dispenser engages with the insert of the port by rotational engagement, the fluid line can be guided downward toward the fluid container together with the insert so that a fluid communication channel with the fluid container is opened.

[0077] Embodiment 21 The method according to Embodiment 20, further comprising the steps of: freezing the transferred fluid in a 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 a fluid dispenser to and from the fluid container; rotating the fluid line within the shell housing of the fluid dispenser and compressing the fluid dispenser so that the fluid line is aseptically inserted into the fluid container; and removing the fluid from the fluid container through the fluid line.

[0078] Embodiment 22 A fluid dispenser connectable to the outer surface of the cap of a fluid container, comprising a body having a first end and a second end, including a fluid line provided between the first end and the second end, and a shell housing provided around the body, wherein the fluid line at the second end of the body is configured to be connectable to an insert provided in the cap by rotating the body, and the shell housing includes a compressible bellows section to allow sterile insertion of the fluid line into the fluid container.

[0079] The examples disclosed herein should be considered in all respects to be illustrative and not limiting. The scope of the invention is indicated not by the foregoing description but rather by the appended claims, which are intended to encompass the meaning of equivalence of claims and all modifications included in the scope.

Claims

1. A sterile, sealed assembly for a fluid container, A cap connectable to the opening of the fluid container, comprising a housing, a cavity within the housing having a support portion, and a first set of seals, A fluid dispenser connectable to the outer surface of the housing of the cap, comprising a body having a first end and a second end, a body having a fluid line provided between the first end and the second end within the body, a shell housing provided around the body, a second set of seals, and an insert connectable to the second end of the body, Equipped with, The main body includes an opening near the second end, which is connected to the fluid line and configured to communicate with the fluid container when the fluid dispenser is connected to the cap. The fluid dispenser is an aseptically sealed assembly configured such that a downward force toward the fluid container causes the insert to fit into the support portion of the cavity, and the insert to be released from the body of the fluid dispenser, thereby sealing the fluid container.

2. The sterile closed assembly according to claim 1, wherein the shell housing comprises a plurality of first retaining mechanisms extending from one end of the shell housing, each configured to engage with a second retaining mechanism provided on the outer surface of the housing of the cap, and the first retaining mechanisms and the second retaining mechanisms have complementary shapes.

3. The sterile closed assembly according to claim 1, wherein the fluid dispenser is provided with an engaging piece for engaging with the insert or engaging member, so that the fluid dispenser can engage with the insert so that the insert can be removed from the support portion of the cavity by rotating the fluid dispenser.

4. The sterile closed assembly according to claim 1, wherein the shell housing comprises an enlarged portion that is in fluid communication with the opening, and when fluid is supplied or removed through the fluid line of the fluid dispenser, the fluid flows from the opening through the enlarged portion and around the insert into the fluid container, or from the fluid container through around the insert and the enlarged portion and then through the opening.

5. The sterile closed assembly according to claim 1, characterized in that the insert is released from the main body by press-fitting it into the cavity and the support portion, and is connected by rotating the fluid dispenser while the insert is fitted into the support portion of the cavity, or both.

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