Integrated sterile system and method for producing the same

Abstract

A bag assembly is provided that includes a sterile system for providing a sterile fluid pathway from the bag assembly to the processing unit. [Solution] The bag assembly 10 includes a bag portion 20 having first walls 22 and second walls 23 defining an interior 26 and an opening 28, the interior being formed by the first and second walls of the bag portion being attached to each other along at least a portion of the periphery of the bag assembly up to one end of the bag portion. The portions of the first and second walls of the bag portion that are not attached to each other form an opening, and the bag assembly also includes a sterile system 40 for sterile connection and disconnection of the bag assembly from a sterilization process, the sterile system being formed continuously at the interface between the sterile system and one end of the bag portion. The sterile system includes an internal passage to allow fluid communication with the interior of the bag portion and the sterilization process.

Description

Technical Field

[0001] The present disclosure generally relates to a bag assembly for containing a fluid. More specifically, the present disclosure relates to a bag assembly including a sterile system for providing a sterile fluid path from the bag assembly to a processing device.

Background Art

[0002] In chemical processes and / or biological processes, it is possible to utilize or produce process materials stored in a storage container, such as a bag, that contains a pharmaceutical fluid or a biological fluid. Tubing materials or other types of couplings and connectors can be utilized to supply the process materials and / or reactants to the storage container. It may be necessary to freeze or keep the process materials at a low temperature within the storage container. Tubing materials or other types of couplings can also be utilized to remove the process materials from the storage container.

Summary of the Invention

[0003] In one embodiment, a bag assembly includes a bag portion having a first wall and a second wall that define an interior and an opening. The interior is formed by the first wall and the second wall of the bag portion being attached to each other along at least a portion of the periphery of the bag assembly to one end of the bag portion. The portions of the first wall and the second wall of the bag portion that are not attached to each other form the opening. The bag assembly also includes a sterile system for sterile connection and disconnection of the bag assembly from a sterilization process, the sterile system being continuously formed at an interface between the sterile system and one end of the bag portion. The sterile system includes an internal passage for enabling fluid communication with the interior of the bag portion and a sterilization process.

[0004] In one embodiment, a fitting is further included. This fitting includes a first outer surface and a second outer surface extending between the two ends, and a fitting extending laterally from the fitting. Continuous formation at the interface is formed by the fitting of the fitting being integrally molded with the sterile system as a single molded product, where an internal passage is formed laterally through the sterile system, the fitting, and the fitting for fluid communication with the interior of the bag portion.

[0005] In one embodiment, a fixture is further included. This fixture includes a first outer surface and a second outer surface extending between the two ends, and a fitting extending laterally from the fixture. Continuous formation at the interface is formed by connecting the fitting of the fixture and the fitting of the fixture, such that the fitting and the sterile system of the fixture are overmolded with a melt-workable material, and the internal passage of the sterile system is connected to an internal passage into the bag portion passing through the fitting and the fixture.

[0006] In one embodiment, the sterile system is formed continuously with the interface and the first and second walls of the bag portion, such that an internal passage is formed through the sterile system so as to connect directly to the interior of the bag portion. In one embodiment, the interface includes a connecting component extending laterally from the sterile system, the outer surface of which is formed continuously with the first and second walls of the bag portion.

[0007] In one embodiment, a method for manufacturing a bag assembly includes forming a bag portion of a bag assembly by attaching a first wall and a second wall together along at least a portion of the periphery of the bag assembly up to at least one end of the bag portion, thereby defining the interior and opening of the bag portion, wherein the portions of the first and second walls of the bag portion that are not attached to each other form an opening. A sterile system is then formed continuously with one end of the bag portion by having a continuously formed interface between the sterile system and the bag portion, and the sterile system is for providing sterile connection and disconnection of the bag assembly from a sterilization process, in which case the sterile system includes an internal passage for fluid communication with the interior of the bag portion and for enabling the sterilization process.

[0008] Refer to the accompanying drawings which form part of this disclosure and illustrate embodiments in which the systems and methods described herein are applicable. [Brief explanation of the drawing]

[0009] [Figure 1] This is a schematic diagram of one embodiment of a low-temperature storage container aseptically connected to a processing device using a continuously formed aseptic system. [Figure 2A] This is an enlarged front perspective view of a continuously formed mounting fixture and sterile system according to one embodiment. [Figure 2B] This is an enlarged cross-sectional view of a continuously formed fixture and sterile system according to one embodiment. [Figure 2C] Figure 2A shows the bottom view of the continuously formed mounting fixture and sterile system attached to the bag portion. [Figure 2D] Figure 2A is a front view of the continuously formed mounting fixture and sterile system attached to the bag portion. [Figure 3] This is an enlarged cross-sectional view of a continuously formed fixture and sterile system according to another embodiment. [Figure 4A]This is a front view of a continuously formed mounting fixture and sterile system according to yet another embodiment. [Figure 4B] This is a front view of a continuously formed mounting fixture and sterile system according to yet another embodiment. [Figure 5] This is a flowchart of a method for manufacturing a bag assembly according to one embodiment. [Modes for carrying out the invention]

[0010] Similar reference numbers represent the same parts throughout the whole.

[0011] This disclosure generally relates to bag assemblies for containing fluids. More specifically, this disclosure relates to bag assemblies including a sterile system for providing a sterile fluid pathway from the bag assembly to a processing device. The term sterile as used herein relates to providing an uninterrupted barrier or fluid pathway that keeps the internal fluid of the bag assembly substantially free of contaminants from the external environment and maintains the sterile state of the internal components.

[0012] Some chemical and / or biological processes utilize or produce process materials that are stored in storage containers, such as bags, that contain drug fluids or biological fluids. Tuning materials or other types of couplings and connectors may be used to supply drug fluids or biological fluids into the storage containers. It may be necessary to freeze or maintain low temperatures within the storage containers. Tuning materials or other types of couplings may also be used to remove drug fluids or biological fluids from the storage containers. Fluids include, but are not limited to, substances that flow or deform when shear stress is applied. Fluids can include, for example, liquids.

[0013] In some cases, drug fluids or biological fluids in storage containers need to be aseptically treated during supply, storage, testing, and / or removal of the drug fluids or biological fluids. That is, the drug fluids or biological fluids are supplied in a sterile environment and are transferable from the storage container under sterile conditions. For example, a thin film, cap, valve, or similar sealing device that maintains a hermetic seal can be attached to and / or coupled to the storage container and / or any processing equipment for aseptic coupling / cutting of the storage container to any processing equipment. The thin film, cap, valve, or similar sealing device can also be perforated, removed, and / or rotated so that the storage container is coupled to the processing equipment and cut using the thin film, cap, automatic shut-off valve, or similar device that enables aseptic cutting functionality, thereby allowing the transfer of sterile drug fluids or biological fluids to the processing equipment.

[0014] Such sterile systems are known in the art. For example, Colder Products Company sells sterile connectors such as AseptiQuik®, Steam-Thru®, and SaniQuik®.

[0015] However, it has been observed that such storage containers, coupled to a sterile system via tubing materials that can use hose barb and tri-clamp coupling systems to connect the storage containers, are stored at extremely low temperatures of -190°C or lower, allowing cryogenic fluids, such as liquid nitrogen or similar substances, to enter the storage containers, causing leakage in the storage containers. Thus, the storage containers are damaged. While we do not wish to be bound by theory, it should be understood that, upon immersion of storage containers in cryogenic fluids, storage containers, tubing materials, and / or sterile systems, which can be made from different materials having different thicknesses and different rates of thermal expansion (and contraction), will contract at different rates and / or have different thermal properties, e.g., rigidity / flexibility. Thus, when storage containers, tubing materials, and sterile systems are immersed in cryogenic fluids, the different contraction rates and / or different thermal properties prevent a bond between the storage containers and the sterile system, thereby allowing nitrogen, in either liquid or gaseous form, to enter the storage containers.

[0016] Figure 1 is a schematic diagram of a bag assembly 10 that overcomes the shortcomings of the prior art. The bag assembly 10 includes a bag portion 20 which is aseptically connected to a processing apparatus 30 using a cryogenic aseptic system 40 that is continuously formed at the interface between the aseptic system 40 and the bag portion 20. The bag assembly 10 is storable in a bag holder 50 in a cryogenic system. The sterilization process may include a processing apparatus 30 which can supply process material, such as a drug fluid or biological fluid, from a sterilization process or sterilization reaction that forms the process material to fill the bag portion 20 and / or the equipment that uses the process material in the bag portion 20 for the sterilization process.

[0017] The bag portion 20 may be a cryogenic fluid storage container. For example, the bag portion 20 includes a first wall 22 and a second wall 23 defining an interior 26 and an opening 28. The interior 26 is formed by the first wall 22 and the second wall 23 being attached to each other along at least a portion of the periphery of the bag portion 20 up to one end of the bag portion 20, where the opening 28 is formed by the portions of the first wall 22 and the second wall 23 of the bag portion 20 that are not attached to each other. In some embodiments, the first wall 22 and the second wall 23 are welded or bonded together along the corresponding edges of these walls along most of the periphery of the bag portion 20 up to one end of the bag portion having the opening 28. Exemplary welding or bonding techniques may include, but are not limited to, thermal bonding, impulse welding, laser welding, ultrasonic welding, platen welding, or similar fusion / fusion welding techniques. It should be noted that the first wall 22 and the second wall 23 of the bag portion 20 are joined to each other without the use of adhesives, solvents, or binders, as this helps maintain the cleanliness of the fluid in the bag assembly by reducing the number of potential sources of leaching and extractability of materials, thereby improving the overall cleanliness of the final assembly.

[0018] Each of the first wall 22 and the second wall 23 of the bag portion 20 can be formed from at least one polymer film, more specifically, from at least one fluoropolymer film. In some embodiments, the fluoropolymer film includes ethylene tetrafluoroethylene (ETFE) polymer, polychlorotrifluoroethylene (PCTFE) polymer, polyvinyl fluoride (PVF) polymer, polyvinylidene fluoride (PVDF) polymer, or a combination thereof. In another embodiment, the fluoropolymer film includes ethylene tetrafluoroethylene (ETFE) polymer, polyvinyl fluoride (PVF) polymer, polyvinylidene fluoride (PVDF) polymer, or a combination thereof. In yet another embodiment, ETFE may be particularly suitable for the construction of the bag assembly. In some embodiments, the first wall 22 and the second wall 23 of the bag portion 20 are formed from a single fluoropolymer film. In a single fluoropolymer film, any intervening layers such as barrier layers, adhesive layers, binding layers, or a combination thereof are excluded. The use of a single fluoropolymer membrane without an intervening layer can reduce the number of potentially leachable or extractable sources, thereby improving the overall cleanliness of the final assembly and the fluids involved in that assembly.

[0019] Each fluoropolymer film forming the first wall 22 and the second wall 23 of the bag portion 20 can have a thickness of approximately 2.5 mils (63.5 μm) to approximately 20 mils (508 μm), or approximately 5 mils (127 μm) to approximately 15 mils (381 μm). In one embodiment, each fluoropolymer film forming the walls 22 and 23 has a thickness of approximately 8 mils (203.2 μm).

[0020] The bag portion 20 is aseptically connected to the cryogenic aseptic system 40 by being continuously formed at the interface between the aseptic system 40 and the bag portion 20. The aseptic system 40 enables the aseptic connection and disconnection of the bag assembly from the sterilization process. The aseptic system 40 includes a first connector / disconnector 42 and a second connector / disconnector 44, where in this case, the first connector / disconnector 42 is fluidly connected to the bag portion 20 and the second connector / disconnector 44 is fluidly connected to the processing device 30. By the coupling of the first connector / disconnector 42 and the second connector / disconnector 44, the fluid passages in the first connector / disconnector 42 and the second connector / disconnector 44 are connected to form a sealed fluid connection that extends laterally through the coupled connectors 42, 44.

[0021] The first connector / disconnector 42 and the second connector / disconnector 44 can be coupled together by any suitable structure for forming a mechanical connector, such as forming a snap fit or press fit. For example, the retaining feature of the first connector / disconnector 42 can be any suitable structure for forming a mechanical connector having a corresponding complementary retaining feature of the second connector / disconnector 44. The retaining feature can include, for example, slots, tabs, flanges, detents, hooks, or any other suitable structure for mechanical engagement with other complementary structures.

[0022] The low-temperature aseptic system 40 can include a pair of removable membranes (not shown) that can seal the laterally formed fluid passage from the ambient environment before the connectors 42, 44 are joined. Each of the removable membranes covers and seals the openings of the first fluid passage and the second fluid passage of each of the connectors 42, 44. The removable membranes are configured to maintain the fluid passage aseptically before the connectors 42, 44 are joined. For example, each thin film prevents contaminants from the environment (such as dust, moisture, etc.) from entering the corresponding fluid passage used to fluidly connect the laterally formed fluid passages in the joined connectors 42, 44. The removable membranes are removed when the connectors 42, 44 are joined. For example, the removable membranes are removed after the space between the joined connectors 42, 44 is compressed.

[0023] The polymer materials of the connectors 42, 44 are generally polymers that are generally non-reactive (e.g., non-reactive with air, non-reactive with the process materials or reactants used in the bag assembly), and materials that are compatible with the bag portion. For example, each of the connectors 42, 44 in one embodiment includes a fluoropolymer that can be dissolved or adhered to, e.g., melted or fused with, the bag portion.

[0024] At least the first connector / disconnector 42 of the sterile system 40 is formed continuously at the interface between the sterile system 40 and one end of the bag portion 20, thereby creating a continuous fluid channel between the sterile system 40 and the bag portion 20. The continuous formation of the sterile system 40 and the bag portion 20 prevents any contaminants from entering the bag assembly from the external environment, especially during cryogenic freezing of the bag assembly, because there are no leak points between the sterile system 40 and the bag portion 20. For example, this continuous formation may be achieved by integrally molding the first connector / disconnector 42 at the interface of the bag portion 20, overmolding the connection between the first connector / disconnector 42 and the bag portion 20 at the interface, or by continuously forming the polymer by directly forming the first connector / disconnector 42 with the bag portion 20 at the interface. In other words, it should be recognized that the bag assembly is formed as a single unit by the continuous formation of the sterile system and the bag portion, without including any intermediate discontinuously formed connecting parts, or by using bonding, melting, or molding processes to bring about a bag assembly without using any clamps between the sterile system and the bag portion. Therefore, even during cryogenic freezing, there are no leakage points between the bag assembly and the sterile system.

[0025] In one embodiment of the present invention, as schematically shown in Figure 1, a first connector / disconnector 42 including a tubular material 60 is formed continuously with the bag portion 20 at an interface. Specifically, a first end of the tubular material 60 is formed continuously with the sterile system 40, thereby connecting the opening of an internal passage in the sterile system 40, for example, an internal passage in the first connector / disconnector 42, to the tubular material 60. The other end of the tubular material 60 is formed continuously with the bag portion 20, in which case the interior of the bag portion 20 is in fluid communication with the sterile system 40 through such interface.

[0026] Figures 2A to 2D illustrate one embodiment of the present invention. In this embodiment, the interface including the tubular material 60 is integrally molded with at least one fitting 200 and at least one sterile system 40. As seen in Figure 2A, the fitting 200 includes a first outer surface 220 and a second outer surface 222 extending between both ends 224, 226 to form a structure that can be attached to the opening 28 of the bag portion 20, for example, by a secondary bonding technique. The fitting 200 is also part of the tubular material 60 and includes at least one fitting 210 extending laterally from the fitting 200, a fitting opening 230 that allows communication between the interior of the bag portion 20 and at least one fitting 210, and at least one first connector / disconnector 42 of the sterile system 40 that is formed in conjunction with at least one fitting 210.

[0027] In this embodiment, the tubular material 60 (at least partially formed by the fitting 210), the fixture 200, and at least one sterile system 40 are integrally molded as a single unit, for example, using a single mold during the molding process, or using injection molding, casting (e.g., two-part casting), thermoforming, etc. Thus, the interface is formed directly with the fixture 200 and the first connector / disconnector 42 of the at least one sterile system 40, or continuously with the polymer.

[0028] As shown in Figure 2B, in one embodiment of the present invention having two different sterile systems, such a structure has a continuous fluid path between the inside of the bag portion and the processing fluid, a flow path through the tubing material / fitting 210, and an internal fluid passage of the first connector / disconnector 42 formed laterally through the sterile system 40, using at least a first connector / disconnector 42 of the sterile system 40 through the fitting opening 230. Thus, the integrally molded fitting and sterile system are formed continuously as a single unit having an internal passage continuously formed so that the inside of the bag portion is in fluid communication with the sterile system. Hence, no additional tubing material or connector is required to connect the sterile system to the bag portion, thereby eliminating a point of leakage between the bag portion 20, the fitting 200, and the sterile system 40, as will be discussed further below. Although the fitting 200 and the first connector / disconnector 42 are discussed above as separate parts, it should be recognized that the fitting and the first connector / disconnector may not be separate elements but may be provided as a single unit secondarily bonded to the bag portion. It should also be noted that, if necessary, a gasket may be provided between the connection of the fixture 200, the pipe material / fitting 210, and the first connector / disconnector 42. The gasket may be press-fitted into the connection or molded onto the fixture, pipe material / fitting, and / or the first connector / disconnector.

[0029] Figures 2C and 2D show the combination of the fixture 200 and the first connector / disconnector 42 attached to the opening 28 of the bag portion 20 between the first wall 22 and the second wall 23. Specifically, the combination of the first outer surface 220 and the second outer surface 222 of the fixture 200 and the first connector / disconnector 42, which extends between both ends 224 and 226, is attached to the first wall 22 and the second wall 23 of the bag portion 20 through the opening 28 of the bag portion 20, thereby creating fluid communication between the combination of the fixture 200 and the first connector / disconnector 42 and the interior 26 of the bag portion 20. The first wall 22 and the second wall 23 of the bag portion 20 are welded or bonded to the combination of the first outer surface 220 and the second outer surface 222 of the fixture 200 and the first connector / disconnector 42, so that a continuous bonded or welded area is formed throughout the periphery of the bag assembly 10. The attachment of the first wall 22 and the second wall 23 along a continuous surface eliminates any weaknesses that might arise, for example, if these walls were bonded to a fixture with sharper edges or a more rounded fixture, resulting in a more robust attachment between the bag portion 20 and the combination of the fixture 200 and the first connector / disconnector 42. The first wall 22 and the second wall 23 of the bag portion 20 can be attached to the combination of the first outer surface 220 and the second outer surface 222 of the fixture 200 and the first connector / disconnector 42 using any suitable bonding or welding technique for a compatible material. For example, the first wall 22 and the second wall 23 of the bag portion 20 may be attached to the combination of the outer surfaces 220, 222 of the fixture 200 and the first connector / disconnector 42 using thermal bonding, laser welding, ultrasonic welding, thermal fusion, or platen welding techniques. In many embodiments, the attachment of the first wall 22 and second wall 23 of the bag portion 20 to the combination of the first outer surface 220 and second outer surface 222 of the fixture 200 and the first connector / disconnector 42 is performed without the use of adhesives, solvents, or binders, thereby reducing the possibility of leaching and extraction in the final bag assembly 10.Therefore, the integrally molded attachment and sterile system combination, as well as the bag portion, are formed continuously as a single unit, thereby eliminating any leakage points between the bag portion 20 and the sterile system 40.

[0030] In one embodiment, the entire fixture 200 is made from a fluoropolymer, which may be a homopolymer or copolymer of fluoropolymers, such as PFA. Thus, the combination of the fixture 200 and the first connector / disconnector 42, as well as the first wall 22 and second wall 23 of the bag portion 20, may be made from one or more of the same polymers to have suitable bonding properties for each other, such as thermal bonding / fusion or melting, similar melting temperature and flow characteristics that allow for chemical resistance or chemical compatibility, and / or UV protection, and other properties required for the application of the fluid confinement system.

[0031] Figure 3 is a perspective view of another embodiment of a bag assembly having a sterile system formed continuously with the bag portion and interface. In this embodiment, at least one fitting 300 includes the fitting 300 and at least one fitting 310 extending laterally from the fitting opening 330. The sterile system 40 is provided separately if the first connector / disconnector 42 includes a connecting component 43 extending laterally from the first connector / disconnector 42. The connecting component 43 includes an internal passage that is in fluid communication with the internal passage of the first connector / disconnector 42 and the sterile system 40.

[0032] In this embodiment, the interface includes a tubular material 60 formed by overmolding a melt-workable material 340 on the connecting component 43 of the first connector / disconnector 42 and the fitting 310 of the fixture 300, in which case the melt-workable material 340 may be a polymer having suitable bonding properties with the fixture 310 and the first connector / disconnector 42, for example, a fluoropolymer or polymer having similar melting temperature and flow rate characteristics that enable thermal bonding / fusion or melting, chemical resistance or chemical compatibility, and / or other properties required for fluid confinement system applications such as UV protection. In many embodiments, the attachment of the melt-workable material 340 to the fixture 300 and the first connector / disconnector 42 is performed without the use of adhesives, solvents, or binders, thereby reducing the possibility of leaching and extractability in the final bag assembly 10.

[0033] As shown in Figure 3, by overmolding a melt-workable material 340 onto the connecting component 43 and fitting 310, the fixture 300 is formed directly with or continuously with a polymer to a first connector / disconnector 42 of at least one sterile system 40. Such a structure has a continuous fluid passage between the interior of the bag portion 20 and the processing fluid, a fixture opening 330, a flow path through the fitting 310, and an internal fluid passage of the first connector / disconnector 42, using at least a first connector / disconnector 42 of the sterile system 40. Thus, the overmolded fixture and sterile system are formed continuously so that the interior of the bag portion is in fluid communication with the sterile system. Therefore, no additional tubing material or connectors are required to connect the sterile system to the bag portion, thereby eliminating a point of leakage between the bag portion 20, the fixture 200, and the sterile system 40. Figure 3 schematically shows the overmolding of the connecting component 43 and fitting 310 as separate parts, but it should be noted that the connecting component 43 can be attached by the barb-type connection of fitting 310.

[0034] Similar to the embodiments described above, the combination of the fixture 300 and the sterile system 40 is then attachable to the opening of the bag portion between the first and second walls of the bag portion (not shown), thereby enabling fluid communication between the fixture 300 and the sterile system 40 and the interior of the bag portion. The first and second walls of the bag portion are weldable or bondable to the first and second outer surfaces of the fixture 300 and the combination of the sterile system 40, thereby forming a continuous bond or weld over the entire periphery of the bag assembly 10. In this case, the first and second walls of the bag portion can be attached to the first and second outer surfaces of the fixture 300 and the combination of the sterile system 40 using any suitable bonding or welding technique, as discussed above. Thus, the overmolded fixture and sterile system are formed continuously, thereby eliminating any leakage points between the bag portion 20 and the sterile system 40.

[0035] Figures 4A and 4B show another embodiment in which the fitting is not used in the continuous formation between the sterile system and the bag portion, as described above. More precisely, the first connector / disconnector 42 of the sterile system 40 is directly connected to the bag portion 20 at the interface, where the internal passage of the first connector / disconnector 42 is directly connected to the interior 26 of the bag portion 20.

[0036] Figure 4A illustrates that the first connector / disconnector 42 is fluidly connected to the interior 26 of the bag portion 20 by being connected between the first wall 22 and the second wall 23 of the bag portion 20, thereby forming a continuous connection with the bag portion 20 at the interface. The first wall 22 and the second wall 23 of the bag portion 20 can be welded or bonded to the outer surface of the first connector / disconnector 42 such that a continuous bond or weld is formed over the entire periphery, and in this case, the first wall 22 and the second wall 23 of the bag portion 20 can also be attached to the outer surface of the first connector / disconnector 42 using any suitable bonding or welding technique discussed above for bonding or welding the fixture to the bag portion.

[0037] By directly connecting the first connector / disconnector 42 at the interface of the bag portion 20, the first connector / disconnector 42 is formed directly with the bag portion 20, continuously with it, or continuously with it by polymer. Such a structure is fluidly connected through an internal fluid passage of the first connector / disconnector 42 formed laterally through the sterile system, thereby enabling fluid communication between the interior of the bag portion 20 and the processing fluid using at least the first connector / disconnector 42 of the sterile system 40. Thus, the sterile system is formed continuously with the bag portion, and there are no leak points between the bag portion 20 and the sterile system 40.

[0038] Figure 4B shows another embodiment in which the first connector / disconnector 42 is fluidly in communication with the interior 26 of the bag portion 20, by forming a continuous interface with the bag portion 20 through which the connecting component 400 of the first connector / disconnector 42 is connected between the first wall 22 and the second wall 23 of the bag portion 20. The first wall 22 and the second wall 23 of the bag portion 20 can be welded or bonded to the outer surface of the connecting component 400 of the first connector / disconnector 42, thereby forming a continuous bond or weld over the entire periphery. In this case, the first wall 22 and the second wall 23 of the bag portion 20 can also be attached to the outer surface of the connecting component 400 of the first connector / disconnector 42 using any suitable bonding or welding technique discussed above for bonding or welding the fixture to the bag portion. It should be noted that the connecting component may be a straight tube and / or have a geometric shape, such as an ellipse, in order to facilitate bonding or welding of the outer surface of the connecting component 400 to the first wall 22 and the second wall 23 of the bag portion 20.

[0039] The first connector / disconnector 42 is formed directly or continuously with the bag portion 20 by directly connecting the connecting component 400 of the first connector / disconnector 42 to the bag portion 20. Such a structure has a continuous flow path between the inside of the bag portion 20 and the processing fluid, by being fluidly connected through the internal fluid passage of the first connector / disconnector 42 formed laterally through the sterile system 40. Thus, the sterile system 40 is formed continuously with the bag portion 20, and there are no leak points between the bag portion 2 and the sterile system 40.

[0040] Therefore, any of the above-described filled bag assemblies 10 are configured to be stored at freezing temperatures (e.g., below 0°C). In one embodiment, the bag assembly 10 is configured to be stored at extremely low temperatures below -150°C. In one embodiment, the bag assembly 10 is configured to be stored at extremely low temperatures below -190°C. In one embodiment, the bag assembly 10 is also reheatable to return to ambient temperature without any substantial deformation. Substantial deformation includes, for example, visible cracking of the material, shrinkage or expansion of this original shape at ambient temperature that may interfere with the joints or adversely affect the sealing of the joints. Low-temperature elastic recovery tests may be performed according to ASTM D1329, ISO 2921, or any other suitable test method for determining suitable shrinkage of the material at the temperatures in which it may be used. Brittleness tests may be performed according to ASTM D2137, ISO 28702, or any other suitable test method for determining crack resistance at the temperatures in which it may be used.

[0041] While we do not wish to be bound by theory, it has been found that, surprisingly, by having a continuous formation between the sterile system and the attachment / bag portion, or by having a continuous polymer formation between the sterile system and the attachment / bag portion, potential leak points are eliminated because there are no connectors or clamps between the bag portion and the sterile system. In this case, at least during the cryogenic freezing process, the sterile system, bag portion, and / or attachment are formed from the same or similar polymer, e.g., a fluoropolymer, having the same or similar thermal shrinkage coefficient and / or thermal properties, so that the sterile system, bag portion, and / or attachment shrink at the same rate and / or have the same or similar thermal properties, thereby eliminating any leak points and having a continuous flow path from the bag portion to the sterile system, the bag assembly can maintain structural integrity and prevent the entry of cryogenic fluids, e.g., nitrogen, into the bag assembly.

[0042] Figure 5 is a flowchart of a method for manufacturing a bag assembly according to one embodiment. In 510, the bag portion is formed by attaching a first wall and a second wall of the bag portion to define the interior and opening. The interior is formed by attaching the first wall and the second wall to each other along at least a portion of the periphery of the bag portion up to one end of the bag portion, where the opening is formed by the portions of the first wall and the second wall of the bag portion that are not attached to each other. Exemplary welding or bonding techniques may include, but are not limited to, thermal bonding, impulse welding, laser welding, ultrasonic welding, platen welding, or similar fusion / fusion welding techniques. It should be noted that the first wall and the second wall of the bag portion are attached to each other without the use of adhesives, solvents, or bonding agents, as this helps maintain fluid cleanliness in the bag assembly by reducing the number of potential sources of leaching and extractability of materials in the construction of the bag assembly, thereby increasing the overall cleanliness of the final assembly.

[0043] At 520, the sterile system is then continuously formed at the interface with the bag portion. The continuous formation of the sterile system with the bag portion may occur as follows:

[0044] A. (In 530) The sterile system is formed continuously at the interface by integrally molding the fixture and the sterile system together as a single molded product. In one embodiment, the fixture and the sterile system are integrally molded by forming the sterile system and the fixture together as a single unit using a single mold during the molding process, or by injection molding, two-part casting, or thermoforming. Thus, the sterile system is in fluid communication with the bag portion through a continuous flow path through the combination of the fixture and the sterile system.

[0045] In 560, the combination of the sterile system and the fitting is then connected to the bag portion. For example, the first and second walls of the bag portion can be welded or bonded to the first and second outer surfaces of the fitting and the combination of the sterile system, thereby forming a continuous bond or weld around the entire periphery of the bag assembly. The first and second walls of the bag portion can be attached to the first and second outer surfaces of the fitting and the combination of the sterile system using any suitable bonding or welding technique. For example, the first and second walls of the bag portion may be attached to the outer surfaces of the fitting and the combination of the sterile system using thermal bonding, laser welding, ultrasonic welding, thermal fusion, or platen welding techniques. In many embodiments, the attachment of the first and second walls of the bag portion to the first and second outer surfaces of the fitting and the combination of the sterile system is performed without the use of adhesives, solvents, or binders, thereby reducing the possibility of leaching and extractability in the final bag assembly. Therefore, the integrally molded attachment and sterile system are formed as a single, continuous unit, and as a result, there are no leakage points between the bag portion and the sterile system.

[0046] B. (In 540) A sterile system is continuously formed at the interface by overmolding a melt-workable material between the fixture and the sterile system. For example, in one embodiment, a tubular material is formed by overmolding a melt-workable material on the connecting component of the first connector / disconnector of the sterile system extending laterally from the first connector / disconnector, and on the fitting of the fixture extending laterally from the fixture, in which case the melt-workable material may be a polymer having suitable bonding properties with the fixture and the first connector / disconnector, e.g., a fluoropolymer or polymer having similar melting temperature and flow rate characteristics that enable thermal bonding / fusion or melting, chemical resistance or chemical compatibility, and / or other properties required for the application of a fluid confinement system, such as UV protection. In many embodiments, the attachment of the melt-workable material to the fixture and the first connector / disconnector is performed without the use of adhesives, solvents, or binders, thereby reducing the possibility of leaching and extractability in the final bag assembly.

[0047] In 560, the combination of the sterile system and the fitting is then connected to the bag portion. For example, the first and second walls of the bag portion can be welded or bonded to the first and second outer surfaces of the fitting and the combination of the sterile system so as to form a continuous bond or weld over the entire periphery of the bag assembly. The first and second walls of the bag portion can be attached to the first and second outer surfaces of the fitting and the combination of the sterile system using any suitable bonding or welding technique. For example, the first and second walls of the bag portion may be attached to the outer surfaces of the fitting and the combination of the sterile system using thermal bonding, laser welding, ultrasonic welding, thermal fusion, or platen welding techniques. In many embodiments, the attachment of the first and second walls of the bag portion to the first and second outer surfaces of the fitting and the combination of the sterile system is performed without the use of adhesives, solvents, or binders, thereby reducing the possibility of leaching and extractability in the final bag assembly. Therefore, the overmolded attachment and sterile system are formed continuously, thereby eliminating any leakage points between the bag portion and the sterile system.

[0048] C. (In 550) The sterile system is formed continuously at the interface by welding or molding the sterile system directly onto the bag portion. In one embodiment, the sterile system is formed continuously with the bag portion at the interface by being directly connected to the first and second walls of the bag portion, thereby the sterile system is in fluid communication with the interior of the bag portion. The first and second walls of the bag portion are weldable or bondable to the outer surface of the sterile system, thereby forming a continuous bond or weld over the entire periphery, in which case the first and second walls of the bag portion can also be attached to the outer surface of the sterile system using any suitable bonding or welding technique discussed above for bonding or welding the fixture to the bag portion.

[0049] In another embodiment, the sterile system is fluidly connected to the interior of the bag portion by being formed continuously with the bag portion at an interface, with a sterile system connector connected between the first and second walls of the bag portion. The first and second walls of the bag portion can be welded or bonded to the outer surface of the sterile system connector, thereby forming a continuous bond or weld over the entire periphery. In this case, the first and second walls of the bag portion can also be attached to the outer surface of the sterile system connector using any suitable bonding or welding technique discussed above for bonding or welding the fixture to the bag portion.

[0050] Optionally, the bag portion is pressurized. Pressurizing the bag portion may be achieved, for example, through a gas pipe that supplies gas through the opening of the bag portion and / or through a sterile system. Pressurizing the bag portion may be done by providing, for example, a gas source such as a gas pipe, or an opening in the mold or apparatus, while the bag portion, sterile system, and / or fixture are inside the mold or ultrasonic welding apparatus. Pressurizing the bag portion causes it to expand.

[0051] The bag assembly is then sterilized after the bag portion, sterile system, and / or fittings are assembled. For example, the bag assembly can be sterilized by gamma irradiation using cobalt-60 to kill microorganisms. The bag assembly may receive gamma irradiation of at least 50 kGy, and up to approximately 100 kGy, 200 kGy, 500 kGy, or 1000 kGy.

[0052] After sterilization, the sterile system is sealed so that the bag assembly remains sterile. In one embodiment, a removable membrane is used to seal the sterile system and maintain the sterility of the fluid passage. It should be noted that other devices, such as valves, caps, or similar devices, can also be used to maintain the sterility of the fluid passage.

[0053] Pattern:

[0054] It should be noted that any one of embodiments 1 to 11 can be combined with any one of embodiments 12 to 17, or 18 or 19. Any one of embodiments 12 to 17 can be combined with any one of embodiments 1 to 11, or 18 or 19.

[0055] Embodiment 1. A bag assembly comprising: a bag portion including a first wall and a second wall defining an interior and an opening, the interior being formed by the first wall and the second wall of the bag portion being attached to each other along at least a portion of the periphery of the bag assembly up to one end of the bag portion, the portions of the first wall and the second wall of the bag portion not attached to each other forming an opening; and a sterile system for sterile connection and disconnection of the bag assembly from a sterilization process, the sterile system being formed continuously at the interface between the sterile system and one end of the bag portion, the sterile system including an internal passage for enabling fluid communication with the interior of the bag portion and a sterilization process.

[0056] Embodiment 2. The bag assembly of Embodiment 1, further comprising a fitting, the fitting including a first outer surface and a second outer surface extending between its two ends, and a fitting extending laterally from the fitting, wherein the continuous formation at the interface is formed by the fitting of the fitting being integrally molded with the sterile system as a single molded product, and an internal passage is formed laterally through the sterile system, the fitting, and the fitting for fluid communication with the interior of the bag portion.

[0057] Embodiment 3. The bag assembly of Embodiment 2, wherein the fixture comprises a fluoropolymer, and the fluoropolymer of the fixture is formed from the same material as the first and second walls of the bag portion.

[0058] Embodiment 4. The bag assembly of Embodiment 1, further comprising a fitting, the fitting comprising a first outer surface and a second outer surface extending between its two ends, and a fitting extending laterally from the fitting, wherein the continuous formation at the interface is formed by connecting the fitting of the fitting and the fitting of the fitting, which are overmolded with a melt-workable material, such that the internal passage of the sterile system is connected to an internal passage into the interior of the bag portion passing through the fitting and the fitting.

[0059] Embodiment 5. The bag assembly of Embodiment 1, wherein the sterile system is formed continuously with the interface and the first and second walls of the bag portion, such that an internal passage is formed through the sterile system so as to connect directly to the inside of the bag portion.

[0060] Embodiment 6. The bag assembly of Embodiment 5, wherein the interface includes a connecting component extending laterally from the sterile system, and the outer surface of the connecting component is formed continuously with the first and second walls of the bag portion.

[0061] Embodiment 7. The bag assembly of Embodiment 6, wherein the connecting component has an elliptical shape.

[0062] Embodiment 8. A bag assembly of any one of Embodiments 5 to 7, wherein the interface includes a first connector / disconnector of a sterile system, the first connector / disconnector being formed in a continuous manner with the first and second walls of the bag portion.

[0063] Embodiment 9. A bag assembly according to any one of Embodiments 1 to 8, wherein the bag assembly is free of adhesives, solvents, binders, or combinations thereof.

[0064] Embodiment 10. A bag assembly according to any of Embodiments 1 to 9, wherein each of the first wall and the second wall comprises at least one fluoropolymer film.

[0065] Embodiment 11. The bag assembly of Embodiment 10, wherein the fluoropolymer membrane comprises an ethylene tetrafluoroethylene polymer.

[0066] Embodiment 12. A method for manufacturing a bag assembly, comprising the steps of: forming a bag portion of a bag assembly by defining the interior and opening of the bag portion by attaching together a first wall and a second wall along at least a portion of the periphery of the bag assembly up to at least one end of the bag portion, wherein the portions of the first wall and the second wall of the bag portion that are not attached to each other form an opening; and forming a sterile system continuously with one end of the bag portion by having an interface continuously formed between the sterile system and the bag portion, wherein the sterile system is for providing sterile connection and disconnection of the bag assembly from a sterilization process, the sterile system including an internal passage for enabling fluid communication with the interior of the bag portion and a sterilization process.

[0067] Embodiment 13. The method of Embodiment 12, wherein a continuously formed interface is formed by integrally molding a fitting extending laterally from the fixture and the sterile system as a single molded product using a single mold, thereby forming an internal passage laterally into the interior of the bag portion through the sterile system, the fitting and the fixture, the method further comprising the step of connecting the fixture to one end of the bag portion.

[0068] Embodiment 14. The continuously formed interface is formed by overmolding a melt-workable material on a connecting component of the sterile system and a fitting extending laterally from the fixture, thereby connecting the internal passage of the sterile system to an internal passage into the bag portion through the fitting and the fixture, the method further comprising the step of connecting the fixture to one end of the bag portion, the method of Embodiment 12.

[0069] Embodiment 15. The method of Embodiment 14, wherein the connecting components of a sterile system, fittings for fixtures, and melt-workable polymer materials are suitable materials for molding.

[0070] Embodiment 16. The method of Embodiment 12, wherein the continuously formed interface is formed by welding a sterile system to the first and second walls of the bag portion, such that an internal passage is formed through the sterile system so as to connect directly to the inside of the bag portion.

[0071] Embodiment 17. The method according to any of Embodiments 12 to 16, wherein each of the first wall and the second wall comprises at least one fluoropolymer film.

[0072] Embodiment 18. An integrated sterile system comprising: a fixture including a first outer surface and a second outer surface extending between its two ends, the fixture including a fluoropolymer; and a sterile system for sterile connection and disconnection from a sterilization process, the sterile system being continuously formed at the interface between the sterile system and the fixture, the sterile system including an internal passage for enabling fluid communication between the fixture and the sterile system.

[0073] Embodiment 19. A bag assembly comprising a bag portion including a first wall and a second wall defining an interior and an opening, the interior being formed by the first wall and the second wall of the bag portion being attached to each other along at least a portion of the periphery of the bag assembly up to one end of the bag portion, the portions of the first wall and the second wall of the bag portion not attached to each other forming an opening, and each of the first wall and the second wall comprising at least one fluoropolymer membrane; and a sterile system for sterile connection and cutting of the bag assembly from a sterilization process, the sterile system comprising an internal passage for enabling fluid communication with the interior of the bag portion and a sterilization process by the continuous formation of polymer formed at the interface between the sterile system and one end of the bag portion.

[0074] The technical terms used herein are intended to describe specific embodiments and are not intended to be limiting. The terms “a,” “an,” and “the” include their plural forms unless otherwise explicitly indicated. The terms “comprises” and “comprising,” when used herein, specify the presence of the described feature, integer, step, operation, element, or component, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, or components.

[0075] With regard to the foregoing description, it should be understood that detailed modifications may be made, in particular, with respect to the constituent materials used, as well as the shape, size, and arrangement of the components, without departing from the scope of this disclosure. The embodiments described herein and described herein are illustrative only, and the true scope and spirit of this disclosure are shown by the following claims.

Claims

1. A bag assembly, A bag portion comprising a first wall and a second wall defining the interior and an opening, wherein the interior is formed by the first wall and the second wall of the bag portion being attached to each other along at least a portion of the periphery of the bag assembly up to one end of the bag portion, and the portions of the first wall and the second wall of the bag portion that are not attached to each other form the opening, A sterile system for sterile joining and cutting of the bag assembly from a sterilization process, comprising a sterile system continuously formed at the interface between the sterile system and one end of the bag portion, The sterile system includes a bag assembly comprising an internal passage for fluid communication between the bag portion and the interior and for enabling the sterilization process.

2. The bag assembly according to claim 1, further comprising a mounting fixture, the mounting fixture comprising a first outer surface and a second outer surface extending between its two ends, and a fitting extending laterally from the mounting fixture, wherein the continuous formation at the interface is formed by the fitting of the mounting fixture being integrally molded with the sterile system as a single molded product, and the internal passage is formed laterally through the sterile system, the fitting, and the mounting fixture for the fluid communication with the interior of the bag portion.

3. The bag assembly according to claim 2, wherein the fitting comprises a fluoropolymer, and the fluoropolymer of the fitting is formed from the same material as the first wall and the second wall of the bag portion.

4. The bag assembly according to claim 1, further comprising a mounting fixture, the mounting fixture comprising a first outer surface and a second outer surface extending between its two ends, and a fitting extending laterally from the mounting fixture, wherein the continuous formation at the interface is formed by overmolding the fitting of the mounting fixture and the sterile system with a melt-workable material, and connecting the sterile system and the fitting of the mounting fixture such that the internal passage of the sterile system is connected to the internal passage to the interior of the bag portion passing through the fitting and the mounting fixture.

5. The bag assembly according to claim 1, wherein the sterile system is formed in a continuous manner with the interface and the first and second walls of the bag portion, such that the internal passage is formed through the sterile system so as to connect directly to the interior of the bag portion.

6. The bag assembly according to claim 5, wherein the interface includes a connecting component extending laterally from the sterile system, and the outer surface of the connecting component is formed continuously with the first wall and the second wall of the bag portion.

7. The bag assembly according to claim 6, wherein the connecting component has an elliptical shape.

8. The bag assembly according to claim 5, wherein the interface includes a first connector / disconnector of the sterile system, and the first connector / disconnector is formed in a continuous manner with the first wall and the second wall of the bag portion.

9. The bag assembly according to claim 1, wherein the bag assembly is free of adhesives, solvents, and binders.

10. The bag assembly according to claim 1, wherein each of the first wall and the second wall comprises at least one fluoropolymer film.

11. A method for manufacturing a bag assembly, A step of forming the bag portion of the bag assembly by attaching a first wall and a second wall together along at least a portion of the peripheral part of the bag assembly up to at least one end of the bag portion, thereby defining the interior and opening of the bag portion, wherein the portions of the first wall and the second wall of the bag portion that are not attached to each other form the opening, The process includes the step of continuously forming a sterile system, wherein the sterile system has an interface continuously formed between the sterile system and the bag portion, and the sterile system is for providing sterile connection and disconnection of the bag assembly from a sterilization process, The sterile system includes an internal passage for fluid communication between the bag portion and the interior and for enabling the sterilization process.

12. The method according to claim 11, wherein the continuously formed interface is formed by integrally molding a fitting extending laterally from the fixture with the sterile system as a single molded product using a single mold, thereby forming the internal passage laterally into the interior of the bag portion through the sterile system, the fitting, and the fixture, the method further comprising the step of connecting the fixture to one end of the bag portion.

13. The method according to claim 11, wherein the continuously formed interface is formed by overmolding a melt-workable material on a connecting component of the sterile system and a fitting extending laterally from the fixture, thereby connecting the internal passage of the sterile system to the internal passage of the bag portion through the fitting and the fixture, the method further comprising the step of connecting the fixture to one end of the bag portion.

14. The method according to claim 13, wherein the connecting component of the sterile system, the fitting of the fixture, and the melt-processable polymer material are moldable materials.

15. The method according to claim 11, wherein the continuously formed interface is formed by welding the sterile system to the first and second walls of the bag portion, such that the internal passage is formed through the sterile system so as to be directly connected to the interior of the bag portion.

16. The method according to claim 11, wherein each of the first wall and the second wall comprises at least one fluoropolymer film.

17. A mounting fixture including a first outer surface and a second outer surface extending between its two endpoints, comprising a fluoropolymer, An integrated sterile system comprising a sterile system for sterile connection and disconnection from a sterilization process, the sterile system being continuously formed by the interface between the sterile system and the fixture, The sterile system is an integrated sterile system that includes an internal passage for enabling fluid communication between the fixture and the sterile system.

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