WO2017189218A2

WO2017189218A2 - Bioprocess bag having plastic tubing with metallized interior channel

Info

Publication number: WO2017189218A2
Application number: PCT/US2017/026885
Authority: WO
Inventors: Adam Joseph Fusco; Natalya Vyacheslavovna ZAYTSEVA
Original assignee: Corning Incorporated
Priority date: 2016-04-29
Filing date: 2017-04-11
Publication date: 2017-11-02
Also published as: WO2017189218A3

Abstract

A bioprocessing bag including a film or laminate and a metal contact layer is provided herein. The bioprocess bag includes a metallic connector having an internal fluid passage, wherein the metallic connector contacts the metal contact layer, and wherein the film or laminate is heat sealed around a portion of the metallic connector to form a hermetically sealed interior compartment. A bioprocessing bag including a metal port fitment having at least one fluid port is also provided herein. The metal port fitment is welded to the metal contact layer to form a hermetically sealed interior compartment. A bioprocessing including a film or laminate having a polymer layer, a metal contact layer, and a plastic port fitment having at least one fluid port is also provided herein. The plastic port fitment is welded to the polymer layer to form a hermetically sealed interior compartment.

Description

BIOPROCESS BAG HAVING PLASTIC TUBING WITH METALLIZED INTERIOR

CHANNEL

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application

Serial No. 62/329,905 filed on April 29, 2016, entitled "BIOPROCESS BAG HAVING PLASTIC TUBING WITH METALLIZED INTERIOR CHANNEL", U.S. Provisional Application Serial No. 62/329,893 filed on April 29, 2016, entitled "BIOPROCESSING BAG HAVING PORT FITMENT", and U.S. Provisional Application Serial No. 62/329,882 filed on April 29, 2016, entitled "BIOPROCESS BAG HAVING METALLIC CONNECTIONS" the contents of which are relied upon and incorporated herein by reference in its entirety.

FIELD

[0002] The present disclosure generally relates to bioprocess bags and systems employing the same. In particular, the present disclosure relates to bioprocess bags having low extractable and leachable materials.

BACKGROUND

[0003] Bags containing fluids under highly sterile conditions are used in the bioprocess industry for the formulation, storage, transfer and transport of fluid while maintaining sterile conditions. Some of the characteristics of the bags to preserve the quality of the products contained within include biocompatability with the products, sterility, and non-pyrogenicity. The bags are typically disposed of after use and are recognized as efficient means to prepare and store sterile fluids. Generally, these disposable bioprocess bags are flexible and made from compatible plastic that is sterilized by Gamma radiation. The bags can be used for ail bioprocess applications including, but not limited to, formulating, filing, storing and transporting final product, stocking pharmaceuticals in cold storage or deep freeze and finally for sampling and analytical purposes. Additionally, the bags may be used for biological fluids such as serum, buffers, and ultrapure water and also for growing cell cultures to obtain the valuable biopharmaceutical compounds produced by cells.

[0004] Fluid processing applications typically employ vessels for at least temporarily receiving and containing the fluid. Such vessels or bags almost universally include one or more ports for use in operations such as introducing or withdrawing a fluid.

[0005] Bioprocess bags typically include a single material or a laminate of materials folded or cut and sealed to provide a container or vessel to hold medium and cells. The bags are generally flexible and disposable. But, while the conventional flexible and disposable bags may be inexpensive and adaptable, such bags may contaminate, to some degree, biological material constituents processed therein via extractables and leachables from the polymers, particularly if the biological materials are caustic or if the processing is done at elevated temperatures, which may impact processing results if the biological materials are sensitive to polymeric extractables and leachables. In addition to the bags themselves, ports, other connectors, or tubing formed from plastic may also serve as a source of polymeric extractables and leachables when fluid and/or biological materials contact the ports, other connectors, or tubing.

SUMMARY

[0006] According to an embodiment of the present disclosure, a bioprocess bag is provided. The bioprocess bag includes a film or laminate, a metal contact layer, and a metallic connector having an internal fluid passage. The metallic connector contacts the metal contact layer, and wherein the film or laminate is heat sealed around a portion of the metallic connector to form a hermetically sealed interior compartment.

[0007] According to an embodiment of the present disclosure, a method of forming a bioprocess bag is provided. The method includes forming a bioprocess bag having a film or laminate. The bioprocess bag also includes a metal contact layer and has at least one opening. The method further includes inserting at least one metallic connector into the at least one opening such that the at least one metallic connector contacts the metal contact layer, and heating the film or laminate to form a heat seal around a portion of the at least one metal connector. [0008] According to an embodiment of the present disclosure, a bioprocess bag is provided. The bioprocess bag includes a film or laminate, a metal contact layer, and at least one metal foil having a fluid passage, wherein the metal foil contacts the metal contact layer and wherein the metal foil is connected to the film or laminate to form a hermetically sealed interior compartment. The bioprocess bag further includes at least one metallic connector having an internal fluid passage, wherein the metallic connector is connected to the metal foil and wherein the internal fluid passage of the metallic connector is fluidly connected to the fluid passage of the metal foil.

[0009] According to an embodiment of the present disclosure, a method of forming a bioprocess bag is provided. The method includes forming a bioprocess bag having a film or laminate. The bioprocess bag also includes a metal contact layer and has at least one opening. The method further includes inserting a first end of at least one metal foil into the at least one opening such that the first end contacts the metal contact layer, the at least one metal foil having a fluid passage. The method further includes connecting a second end of the at least one metal foil to a metallic connector having an internal fluid passage, wherein connecting the second end of the at least one metal foil to a metallic connector fluidly connects the fluid passage of the at least one metal foil to the internal fluid passage of the at least one metallic connector. The method further includes connecting the metal foil to the film or laminate to seal the at least one opening.

[0010] According to an embodiment of the present disclosure, a bioprocessing bag is provided herein. The bioprocessing bag includes a film or laminate, a metal contact layer, and a metal port fitment having at least one fluid port. The metal port fitment is welded to the metal contact layer to form a hermetically sealed interior compartment.

[0011] According to an embodiment of the present disclosure, a method of forming a bioprocess bag is provided. The method includes forming a bioprocessing bag having a film or laminate and a metal contact layer, the bioprocessing bag having an opening. The method further includes inserting a metal port fitment into the opening, heating the film or laminate, and welding the metal contact layer to the metal port fitment to form a hermetically sealed interior compartment. [0012] According to an embodiment of the present disclosure, a bioprocessing bag is provided herein. The bioprocessing bag includes a film or laminate having a polymer layer, a metal contact layer, and a plastic port fitment having at least one fluid port. The plastic port fitment is welded to the polymer layer to form a hermetically sealed interior compartment.

[0013] According to an embodiment of the present disclosure, a method of forming a bioprocess bag is provided. The method includes forming a bioprocessing bag having a film or laminate having a polymer layer, the bioprocessing bag further including a metal contact layer and an opening. The method further includes inserting a plastic port fitment into the opening, heating the film or laminate, and welding the polymer layer to the plastic port fitment to form a hermetically sealed interior compartment.

[0014] According to an embodiment of the present disclosure, a bioprocess bag is provided. The bioprocess bag includes a film or laminate, a metal contact layer, and at least one connection apparatus having at least one internal fluid passage. The bioprocess bag also includes at least one tube connected to the at least one connection apparatus and including a metal coating or laminate disposed on an interior wall of the at least one tube.

[0015] Additional features and advantages will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from that description or recognized by practicing the embodiments as described herein, including the detailed description which follows, the claims, as well as the appended drawings.

[0016] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary, and are intended to provide an overview or framework to understanding the nature and character of the claims. The accompanying drawings are included to provide a further understanding, and are incorporated in and constitute a part of this specification. The drawings illustrate one or more embodiment(s), and together with the description serve to explain principles and operation of the various embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The disclosure will be understood more clearly from the following description and from the accompanying figures, given purely by way of non-limiting example, in which:

[0018] Figure 1 illustrates an exploded view of an exemplary bioprocess bag in accordance with embodiments of the present disclosure;

[0019] Figure 2 illustrates an exploded view of an exemplary bioprocess bag in accordance with embodiments of the present disclosure;

[0020] Figure 3 illustrates an exemplary bioprocess bag in accordance with embodiments of the present disclosure;

[0021] Figure 4 illustrates an exemplary bioprocess bag in accordance with embodiments of the present disclosure;

[0022] Figure 5 illustrates an exemplary port fitment in accordance with embodiments of the present disclosure;

[0023] Figure 6 illustrates a cross section of an exemplary port fitment in accordance with embodiments of the present disclosure;

[0024] Figure 7 an exemplary metallic connector in a bioprocess bag in accordance with embodiments of the present disclosure;

[0025] Figure 8 an exemplary metallic connector in a bioprocess bag in accordance with embodiments of the present disclosure; and

[0026] Figure 9 is a cross section of a tube having a metal coating or laminate on at least a portion of the interior wall. DETAILED DESCRIPTION

[0027] Reference will now be made in detail to the present embodiment(s), an example(s) of which is/are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts.

[0028] The singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. The endpoints of all ranges reciting the same characteristic are independently combinable and inclusive of the recited endpoint. All references are incorporated herein by reference.

[0029] As used herein, "have," "having," "include," "including," "comprise,"

"comprising" or the like are used in their open ended sense, and generally mean "including, but not limited to. "

[0030] All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

[0031] The present disclosure is described below, at first generally, then in detail on the basis of several exemplary embodiments. The features shown in combination with one another in the individual exemplary embodiments do not all have to be realized. In particular, individual features may also be omitted or combined in some other way with other features shown of the same exemplary embodiment or else of other exemplary embodiments.

[0032] Embodiments of the present disclosure relate to bioprocess bags that include low extractable and leachable materials and methods for forming such bioprocess bags. Bioprocess bags in accordance with embodiments of the present disclosure are formed from disposable materials and may be discarded after a single use, thereby eliminating washing/sterilizing operations as well as maintenance associated with conventional bioprocess vessels. Bioprocess bags described herein include tubing, tubing connectors and tubing manifold portions that of fluids and/or other components into or out of an interior compartment of the bioprocess bag. Provided herein are bag designs and methods for forming bioprocess bags that provide at least one of: cost benefits, ease of manufacture and reduction in the level of extractable and leachable materials to which fluid and/or other components are exposed in conventional plastic bioprocess bags.

[0033] Figures 1 -2 illustrate an exploded view of an exemplary bioprocess bag in accordance with embodiments of the present disclosure. As shown, the bioprocess bag 100 includes at least two sheets 102, 104 formed from films or laminates. The sheets 102, 104 may be welded along the edges of the sheets to form a pillow-shaped bag having an interior compartment for receiving fluid. Alternatively, as shown in Figures 3-4, the bioprocess bag 200 may be a three-dimensional bag having a bottom portion 202, a top portion 204 and a sidewall 280 which define an interior compartment for receiving fluid. At least one of the bottom portion 202, the top portion 204 and the sidewall 280 is formed from a film or laminate. The sidewall 280 may be formed from a single continuous piece of material. Alternatively, the sidewall 280 may include two or more panels joined along edges thereof. The sidewall 280 and/or the bottom portion 202 and/or the top portion 204 may be formed from a single piece of material whereby boundaries of the various portions of the bioprocess bag 200 are defined by folds or creases. Alternatively, one or more of the sidewall 280, the bottom portion 202 and the top portion 204 may be formed separately and joined along edges thereof such as by welding the portions together. The bioprocess bag 100, 200 is hermetically sealed and preferably provides a closed system for use in all phases of processing fluid and/or other components. As used herein, the term "closed system" refers to a system sealed to ensure sterility of the contents of the system and to limit or prevent the introduction of contaminants from the surrounding atmosphere.

[0034] Each of the sheets 102, 104 of the bioprocess bag 100 may be formed from one or more of the same or different materials. Each of the top portion 204, the bottom portion 202 and the sidewall 280 of the bioprocess bag 200 may be formed from one or more of the same or different materials. Where opaque or colored materials are used, at least a portion of the bag may be substantially clear to allow for viewing of fluid and/or other components in the interior compartment of the bag. For example, a portion of any of sheets 102, 104 or at least a portion of any of top portion 204, bottom portion 202 and the sidewall 280 may be clear to provide a window through which the interior compartment of the bag can be viewed.

[0035] As used herein, the term "fluid" is used to denote any substance capable of flowing, such as liquids, liquid suspensions, gases, gaseous suspensions, or the like, without limitation. The term "fluid and/or other components" is used throughout the present disclosure to refer to fluid which may include cell culture media having nutrients for cell growth, cells, byproducts of the cell culture process, and any other biological materials or components that may conventionally be added or formed in a bioprocess system. Bioprocess bags and other vessels described herein may include one or more cells or reagents. Additionally, the bags may include cell culture media. Cell culture media may be for example, but is not limited to, sugars, salts, amino acids, serum (e.g., fetal bovine serum), antibiotics, growth factors, differentiation factors, colorant, or other desired factors. Common culture media that may be provided in the bag includes Dulbecco's Modified Eagle Medium (DMEM), Ham's F12 Nutrient Mixture, Minimum Essential Media (MEM), RPMI Medium, and the like. Any type of cultured cell may be included in the bag including, but not limited to, immortalized cells, primary culture cells, cancer cells, stem cells (e.g., embryonic or induced pluripotent), etc. The cells may be mammalian cells, avian cells, piscine cells, etc. The cells may be of any tissue type including, but not limited to, kidney, fibroblast, breast, skin, brain, ovary, lung, bone, nerve, muscle, cardiac, colorectal, pancreas, immune (e.g., B cell), blood, etc. The cells may be in any cultured form in the bag including disperse (e.g., freshly seeded), confluent, 2-dimensional, 3 -dimensional, spheroid, etc. In some embodiments, cells are present without media (e.g., freeze-dried, in preservative, frozen, etc.).

[0036] The bioprocess bag 100, 200 may be formed from materials that are conventionally associated with disposable products for bioprocess applications. Any or all of the sheets 102, 104 of the bioprocess bag 100, or the bottom portion 202, top portion 204 and sidewall 280 of the bioprocess bag 200, may be formed from a film or laminate that includes at least one plastic material from the following group: polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephtalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), poly ether ether ketone (PEEK) polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA) and derivatives thereof. According to embodiments of the present disclosure, at least a portion of the film or laminate may include at least one metallic layer of a metal such as, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides. Non-limiting examples of stainless steel include 200-series, 300-series, 400-series and 500-series, including the grades 201, 202, 301, 302, 303, 304, 305, 308, 309, 310, 314, 316, 316L, 321, 347, 348, 403, 209, 410, 416, 420, 429, 430, 431, 434, 44, 442, 446, 501 and 502. The at least one metallic layer may be included in the film or laminate as a non-contact layer (i.e: the at least one metallic layer does not contact fluid and/or other components in the interior compartment of the bag) and may serve as a metal gas barrier layer. Alternatively, the at least one metallic layer may be included in the film or laminate as a metal contact layer (i.e: the at least one metallic layer does not contact fluid and/or other components in the interior compartment of the bag) and may serve as a low extractable and leachable contact layer. The at least one metallic layer may include a metal oxide surface. The metal oxide surface may include the same or a different metal than the metal of the at least one metallic layer. The at least one metallic layer may also include aluminum metal or aluminum metal alloys having a passivating oxide (corrosion resistant) surface layer. In some such embodiments, the at least one metallic layer may be formed from a bio-inert metal and/or metal oxide; where, for example, the metal and/or metal oxide resists corrosion from aldehydes and amines, as may be present in the fluid and/or other components in the interior compartment of the bag. The metal and/or metal oxide may resist corrosion to aqueous buffer solutions (for example phosphate or tris buffers) and/or aqueous saline solutions. As used herein, the term "resists corrosion" refers to the bio-inert metal oxidizes at a rate of less than or equal to 1000 nanometers (nm) depth in 24 hours at 50 degrees Celsius (°C) in deionized water, such as less than or equal to 100 nm depth, and in some embodiments less than or equal to 10 nm depth in 24 hours at 50°C in deionized water.

[0037] As an alternative to at least a portion of the film or laminate including at least one metallic layer, a metal contact layer separate from the film or laminate may include metal sheets disposed in the interior compartment of the bioprocess bag 100, 200, where the sheets form an interior compartment for receiving fluid. In a pillow-shaped bag, the edge of the metal sheets may be circumferentially sealed to form a pouch. Alternatively, the sheets may not be sealed or otherwise connected to each other. A three-dimensional bag may include metal sheets complimentary to the bottom portion 202, the top portion 204 and the sidewall 280 of the bioprocess bag 200 with the metal sheets being joined along edges thereof such as by welding the sheets together.

[0038] It should be understood that the dimensions of the bioprocess bag 100, 200 including both relative and absolute dimensions can be varied. For example, the bags may be configured to hold a volume of fluid and/or other components of about 1.0 ml, or about 5.0 ml, or about 10 ml, or about 25 ml, or about 50 ml, or about 100 ml, or about or about 250 ml, or about 500 ml, or about 1000 ml, or about 2000 ml, or about 5000 ml, or about 10,000 ml, or even about 20,000 ml, as well as all volumes therein between.

[0039] Bioprocess bags 100, 200 as described herein include at least one connection apparatus which includes an internal fluid passage that permits the flow of fluids and/or other components into or out of an interior compartment of the bioprocess bag 100, 200. As shown in Figures 1-2, and in more detail in Figures 5-6, the at least one connection apparatus may be a port fitment 40 having at least one port 42 that permits the flow of fluids and/or other components into or out of an interior compartment of the bioprocess bag 100, 200. The at least one port 42 is in fluid communication with an interior passage of an extension 44 that extends a predetermined length from an opening of the at least one port 42 and is configured to engage an open end of a length of tubing. The extension 44 may include a coupler, such as a barb, at one end to facilitate engagement with an open end of tubing. The port fitment 40 may include a plurality of ports 42. The dimensions of the plurality of ports 42 may be equal for each of the plurality of ports 42, or the dimensions of each of the plurality of ports 42 may vary. It is also contemplated that the dimensions of at least two of the plurality of ports 42 may be equal and at least one other of the plurality of ports 42 differs from the dimensions of the at least two of the plurality of ports 42.

[0040] According to embodiments of the present disclosure, the port fitment 40 may be any shape. The exemplary port fitment 40 illustrated in the figures is a boat shaped port fitment, but the port fitment 42 disclosed herein is not so limited. The port fitment 40 may be a plastic port fitment formed from, for example, but not limited to, high density polypropylene (HDPE), polypropylene, EVA, LDPE and LLDPE. Alternatively, the port fitment 40 may be a metal port fitment formed from, for example, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides.

[0041] Where the port fitment 40 is a plastic port fitment, connection is formed between a polymer layer of the film or laminate of the bioprocess bag 100, 200 and the port fitment 40 to form a hermetic seal between the bag and the port fitment 40. Where the port fitment 40 is a metal port fitment, connection is formed between a metallic layer of the film or laminate of the bioprocess bag 100, 200 and the port fitment 40 to form a hermetic seal between the bag and the port fitment 40. As shown in Figure 6, the port fitment 40 includes an exterior surface 54 and an interior surface 52. Connection between the bioprocess bag 100, 200 and the port fitment 40 may be along any one of the exterior surface 54 and the interior surface 52. Where the port fitment 40 is a plastic port fitment and the film or laminate includes a metal contact layer, an outer polymer layer of the film or laminate may be connected to the interior surface 52 of the port fitment 40. Alternatively, the film or laminate may include a partial metal contact layer where a portion of the polymer layer is not covered by the metal contact layer. The portion of the polymer layer not covered by the metal contact layer may be connected to the exterior surface 54 of the port fitment 40. The connection may be made by welding or any other type of attachment, such that, with the exception of the at least one port 42, a fluid-impervious seal is formed between the port fitment 40 and the bioprocess bag 100, 200.

[0042] The plastic port fitment described herein may also include at least one metalized surface. Referring again to Figure 6, the port fitment 40 includes an interior surface 52, and the extension 44 includes an interior surface 46. At least one of interior surface 52 and interior surface 46 may be a coated with at least one metal such as, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides. As described in more detail below, the metal coating is applied to the plastic port fitment by a metallization process. A plastic port fitment having at least one metalized surface may be more easily connected to a polymer layer of the film or laminate. Additionally, metalized interior surfaces 46, 52 may reduce the amount of plastic contacted by fluid and/or other components when entering or exiting the interior compartment of the bag and may serve as low extractable and leachable components of a bioprocess bag 100, 200 in accordance with embodiments of the present disclosure.

[0043] Embodiments of the present disclosure also relate to methods of forming bioprocess bags as described herein. The method includes forming a bioprocess bag from a film or laminate, wherein the bioprocess bag has an opening. Forming the bioprocess bag may include connecting at least two sheets 102, 104 formed from films or laminates as described herein by welding along edges of the sheets 102, 104 to form a pillow-shaped bag having an interior compartment for receiving fluid. Alternatively, forming the bioprocess bag may include forming a three-dimensional bag having a bottom portion 202, a top portion 204 and a sidewall 280 which define an interior compartment for receiving fluid. At least one of the bottom portion 202, a top portion 204 and a sidewall 280 is formed from films or laminates as described herein. One or more of the sidewall 280, the bottom portion 202 and the top portion 204 may be formed separately and joined along edges thereof such as by welding the portions together. Forming the bioprocess bag includes leaving a portion of the material of the bag unconnected such that the bag has an opening. For example, where forming the bioprocess bag includes connecting at least two sheets 102, 104 formed from films or laminates by welding along edges of the sheets 102, 104, a portion of the edges of the sheets 102, 104 would not be welded together.

[0044] Forming a bioprocess bag may include forming the bag from a film or laminate including a metal contact layer and/or a polymer layer. Alternatively, forming a bioprocess bag may include forming a metal contact layer separate from the film or laminate by disposing metal sheets in the interior compartment of the bioprocess bag 100, 200, where the sheets form the interior compartment for receiving fluid. In a pillow-shaped bag, the method may include sealing the edge of the metal sheets to form a pouch. Alternatively, the sheets may not be sealed or otherwise connected to each other. In a three-dimensional bag, the method may include joining the metal sheets along edges thereof such as by welding to form metal sheets complimentary to the bottom portion 202, the top portion 204 and the sidewall 280 of the bioprocess bag 200.

[0045] According to embodiments of the present disclosure, the method further includes inserting a port fitment into the opening of the bioprocess bag. The port fitment 40 may be a plastic port fitment or a metal port fitment as described herein. Inserting the port fitment 40 includes contacting the film or laminate material of the bioprocess bag 100, 200 near the opening with a surface of the port fitment 40. The surface of the port fitment 40 may be any one of the exterior surface 54 and the interior surface 52 of the port fitment 40. The method further includes heating the film or laminate material and welding the film or laminate material to the port fitment 40 to form a hermetically sealed interior compartment. Where the port fitment 40 is a plastic port fitment, welding the film or laminate material to the port fitment 40 includes welding a polymer layer of the film or laminate of the bioprocess bag 100, 200 to the port fitment 40. Where the port fitment 40 is a metal port fitment, welding the film or laminate material to the port fitment 40 includes welding a metallic layer of the film or laminate of the bioprocess bag 100, 200 to the port fitment 40.

[0046] Embodiments of the present disclosure may also include metallizing a portion of an interior surface of the port fitment. Where the port fitment 40 is a plastic port fitment, metallizing a portion of the interior surface of the port fitment 40 includes coating the portion of the interior surface with a metal such as, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides. The portion of the interior surface of the port fitment of the port fitment 40 may be interior surface 52 of the port fitment 40, or the interior surface 46 of the extension 44. Metallizing a portion of an interior surface of the port fitment 40 may include coating the interior surface using any known metallization process. The metallization process may be, for example, but not limited to, vacuum metallization, arc spraying, flame spraying, electroless plating or electroplating. The metallization process may be controlled through the use of masks or other conventional techniques to limit metallization to an interior surface of the port fitment 40. [0047] As shown in Figures 3-4, and in more detail in Figures 7-8, at least one connection apparatus may be at least one metallic connector 140 which includes an internal fluid passage that permits the flow of fluids and/or other components into or out of an interior compartment of the bioprocess bag 100, 200. The at least one metallic connector 140 includes a proximal end and a distal end and extends a predetermined length from an opening in the bioprocess bag 100, 200. The proximal end of the at least one metallic connector 140 may be connected to the metal contact layer, or may extend through an opening in the metal contact layer and into the interior compartment of the bioprocess bag 100, 200. Alternatively, the proximal end of the at least one metallic connector 140 may be connected to a foil sheet 160 which is in turn connected to the metal contact layer. The foil sheet 160 forms a passage that fluidly connects the interior compartment of the bioprocess bag 100, 200 to the internal fluid passage of the at least one metallic connector 140. The distal end of the at least one metallic connector 140 is configured to engage an open end of a length of tubing. The at least one metallic connector 140 may be formed from, for example, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides.

[0048] The bioprocess bag 100, 200 may include a plurality of metallic connectors 140.

The dimensions of the plurality of metallic connectors 140 may be equal, or the dimensions of each of the plurality of metallic connectors 140 may vary. It is also contemplated that the dimensions of at least two of the plurality of metallic connectors 140 may be equal and at least one other of the plurality of metallic connectors 140 differs from the dimensions of the at least two of the plurality of metallic connectors 140. As shown in Figure 7, the at least one metallic connector 140 may include a coupler 150 configured to hold the at least one metallic connector 140 in the bioprocess bag 100, 200. The coupler 150 may be a portion having any shape that extends from an outer wall of the at least one connector 140 around which portions of the film or laminate of the bioprocess bag 100, 200 may be heat sealed. The coupler 150 may be, for example, a metal barb, a metal or plastic ring, or a metal or plastic flange. The coupler 150 may be integrally formed with the at least one metallic connector 140 or may be separately formed and attached to the at least one metallic connector 140. [0049] Figure 7 illustrates an exemplary bioprocess bag in accordance with embodiments of the present disclosure. As shown, the at least one metallic connector 140 extends into an opening of the bioprocess bag 100, 200, contacts the metal contact layer and fluidly connects the interior compartment to the exterior of the bag. The bioprocess bag 100, 200 includes an opening for each of the at least one metallic connector 140. The opening is an edge portion of the bioprocess bag 100, 200 where the sheets of the film or laminate are not welded together. The at least one metallic connector 140 extends through the opening and into the interior compartment of the bioprocess bag 100, 200. The film or laminate is heat sealed around a portion of the at least one metallic connector 140 which holds the at least one metallic connector 140 relatively stationary, and which, with the exception of the internal fluid passage of the at least one metallic connector 140, forms a fluid- impervious seal between the bag and the at least one metallic connector 140. Optionally, the at least one metallic connector 140 may be connected to the metal contact layer, such as through a weld or an adhesive.

[0050] Figure 8 illustrates an exemplary bioprocess bag in accordance with embodiments of the present disclosure. As shown, the at least one metallic connector 140 is connected to a foil sheet 160 which extends from an opening in the bioprocess bag 100, 200. The at least one metallic connector 140 may be connected to the foil sheet 160 through an adhesive layer provided on the foil sheet 160. The foil sheet 160 contacts the metal contact layer and forms a passage that fluidly connects the interior compartment of the bioprocess bag 100, 200 to the internal fluid passage of the at least one metallic connector 140. Similar to Figure 7, the bioprocess bag 100, 200 includes an opening for each foil sheet 160 which corresponds to each of the at least one metallic connector 140. The opening is an edge portion of the bioprocess bag 100, 200 where the sheets of the film or laminate are not welded together. The foil sheet 160 extends through the opening and into the interior compartment of the bioprocess bag 100, 200. The foil sheet 160 may be connected to the film or laminate, such as by an adhesive, such that the opening is closed. The adhesive is preferably a material that is capable of joining a metal and a plastic material. The film or laminate holds the foil sheet 160 relatively stationary, and, with the exception of the fluid passage of the foil sheet 160, forms a fluid- impervious seal between the bag and the foil sheet 160. Optionally, the foil sheet 160 may be connected to the metal contact layer, such as through a weld or an adhesive. The foil sheet 160 may formed from, for example, but not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides.

[0051] Embodiments of the present disclosure also relate to methods of forming bioprocess bags as described herein. The method includes forming a bioprocess bag from a film or laminate, wherein the bioprocess bag has at least one opening. Forming the bioprocess bag may include connecting at least two sheets 102, 104 formed from films or laminates as described herein by welding along edges of the sheets 102, 104 to form a pillow-shaped bag having an interior compartment for receiving fluid. Alternatively, forming the bioprocess bag may include forming a three-dimensional bag having a bottom portion 202, a top portion 204 and a sidewall 280 which define an interior compartment for receiving fluid. At least one of the bottom portion 202, a top portion 204 and a sidewall 280 is formed from films or laminates as described herein. One or more of the sidewall 280, the bottom portion 202 and the top portion 204 may be formed separately and joined along edges thereof such as by welding the portions together. Forming the bioprocess bag includes leaving a portion of the material of the bag unconnected such that the bag has an opening. For example, where forming the bioprocess bag includes connecting at least two sheets 102, 104 formed from films or laminates by welding along edges of the sheets 102, 104, a portion of the edges of the sheets 102, 104 would not be welded together.

[0052] Forming a bioprocess bag may include forming the bag from a film or laminate including a metal contact layer and/or a polymer layer. Alternatively, forming a bioprocess bag may include forming a metal contact layer separate from the film or laminate by disposing metal sheets in the interior compartment of the bioprocess bag 100, 200, where the sheets form the interior compartment for receiving fluid. In a pillow-shaped bag, the method may include sealing the edge of the metal sheets to form a pouch. Alternatively, the sheets may not be sealed or otherwise connected to each other. In a three-dimensional bag, the method may include joining the metal sheets along edges thereof such as by welding to form metal sheets complimentary to the bottom portion 202, the top portion 204 and the sidewall 280 of the bioprocess bag 200. [0053] According to embodiments of the present disclosure, the method further includes inserting at least one metallic connector into the at least one opening of the bioprocess bag. Inserting the at least one metallic connector 140 includes contacting the film or laminate material of the bioprocess bag 100, 200 near the opening with a surface of the at least one metallic connector 140 and also includes contacting a portion of the metal contact layer with a surface of the at least one metallic connector 140. The method further includes heating the film or laminate material to form a heat seal around the at least one metal connector 140.

[0054] Alternatively, the method may include inserting a first end of at least one metal foil into the at least one opening of the bioprocess bag and connecting a second end of the metal foil to a metallic connector. Inserting the at least one metal foil 160 includes contacting the film or laminate material of the bioprocess bag 100, 200 near the opening with a surface of the at least one metal foil 160 and also includes contacting a portion of the metal contact layer with a surface of the at least one metal foil 160. Connecting the at least one metal foil 160 to the at least one metallic connector 140 may include joining the metal foil 160 to the metallic connector 140 such as with an adhesive. The method further includes connecting the metal foil 160 to the film or laminate, such as by joining the metal foil 160 to the film or laminate with an adhesive on the metal foil 160.

[0055] The bioprocess bag 100, 200 may include tubes fluidly connected to an interior compartment of the bioprocess bag 100, 200 through at least one connection apparatus, such as through a port fitment 40, an at least one metallic connector 140, or any other connection which includes an internal fluid passage that permits the flow of fluids and/or other components into or out of an interior compartment of the bioprocess bag 100, 200. Figure 9 shows a cross section of a portion of a tube 300 having an elongate wall 310 defining an interior channel 312 configured to transport fluid and/or other components. The tube 300 includes open ends configured to engage a connection apparatus on the bioprocess bag 100, 200. The tube 300 may have a circular cross-section or a cross-section having another shape, such as oval or oblong, for example. The tube 300 includes a plastic portion 320 having a thickness. The plastic portion 320 may be formed from at least one polymer material from the following group polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), very low density polyethylene (VLDPE), ethylene vinyl acetate co-polymers (EVA) or combinations thereof. The plastic portion 320 is preferably a highly inert and flexible sterile material conventionally used in bioprocess applications.

[0056] The plastic portion 320 includes an interior wall which defines the interior channel 312. At least a portion of the interior wall of the plastic portion 320 includes a metal coating or laminate 330 having a thickness. The metal coating or laminate 330 may be, for example, but is not limited to, stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and/or oxides thereof (including alloys thereof), or other metals and/or metal oxides. The metal coating or laminate 330 may be applied to the interior wall of the plastic portion 320 using conventional deposition processes. For example, the metal coating or laminate may be applied using sputtering techniques, metallization techniques, or spraying techniques. The metal coating or laminate 330 may be a layer attached to the interior wall of the plastic portion 320 using at least one adhesive or through chemically bonding the metal coating or laminate 330 to the plastic portion 320. Alternatively, plastic material may be overlaid on a strip of metal material and the strips may be manipulated to a predetermined shape to form tubing having an elongate wall by bringing opposite edges of the metal strip into contact and opposite edges of the plastic strip into contact and the edges connected to form a seam. Once connected the strip of metal material forms the coating or laminate 330 and the strip of plastic forms the plastic portion 320. The metal coating or laminate 330 serves as a low extractable and leachable contact layer and reduces the level of extractable and leachable materials to which fluid and/or other components are exposed.

[0057] Tubes 300 as described herein may connect the bioprocess bag 100, 200 to external bioprocess vessels. The bioprocess vessels may be any type of bag or vessel used for any bioprocess applications including, but not limited to, formulating, filing, storing and transporting final product, stocking pharmaceuticals in cold storage or deep freeze and finally for sampling and analytical purposes. The tube 300 may also connect the bioprocess bag 100, 200 to a tubing manifold which include a plurality of ports configured to connect a plurality of bioprocess vessels via a plurality of tubes 300. [0058] According to an aspect (1) of the present disclosure, a bioprocess bag is provided.

The bioprocess bag comprises: a film or laminate; a metal contact layer; and a metallic connector comprising an internal fluid passage, wherein the metallic connector contacts the metal contact layer, and wherein the film or laminate is heat sealed around a portion of the metallic connector to form a hermetically sealed interior compartment.

[0059] According to an aspect (2) of the present disclosure, the bioprocess bag of aspect

(1) is provided wherein a portion of the metallic connector is connected to the metal contact layer.

[0060] According to an aspect (3) of the present disclosure, the bioprocess bag of any of aspects (l)-(2) is provided comprising a plurality of metallic connectors.

[0061] According to an aspect (4) of the present disclosure, a bioprocess bag is provided.

The bioprocess bag comprises: a film or laminate; a metal contact layer; at least one metal foil comprising a fluid passage, wherein the metal foil contacts the metal contact layer and wherein the metal foil is connected to the film or laminate to form a hermetically sealed interior compartment; and at least one metallic connector comprising an internal fluid passage, wherein the metallic connector is connected to the metal foil and wherein the internal fluid passage of the metallic connector is fluidly connected to the fluid passage of the metal foil.

[0062] According to an aspect (5) of the present disclosure, the bioprocess bag of aspect

(4) is provided further comprising an adhesive which connects the metal foil to the portion of the metallic connector.

[0063] According to an aspect (6) of the present disclosure, the bioprocess bag of any of aspects (4)-(5) is provided further comprising an adhesive which connects the metal foil to the film or laminate.

[0064] According to an aspect (7) of the present disclosure, the bioprocess bag of any of aspects (4)-(6) is provided comprising a plurality of metal foils and a plurality of metallic connectors. [0065] According to an aspect (8) of the present disclosure, the bioprocess bag of any of aspects (4)-(7) is provided, wherein the metallic connector comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[0066] According to an aspect (9) of the present disclosure, a bioprocess bag is provided.

The bioprocess bag comprises: a film or laminate; a metal contact layer; and a metal port fitment comprising at least one fluid port, wherein the metal port fitment is welded to the metal contact layer to form a hermetically sealed interior compartment.

[0067] According to an aspect (10) of the present disclosure, the bioprocess bag of aspect

(9) is provided wherein the metal contact layer is welded to an exterior surface of the metal port fitment.

[0068] According to an aspect (11) of the present disclosure, the bioprocess bag of aspect

(9) is provided, wherein the metal contact layer is welded to an interior surface of the metal port fitment.

[0069] According to an aspect (12) of the present disclosure, the bioprocess bag of any of aspects (9)-(l 1) is provided, wherein the metal port fitment comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[0070] According to an aspect (13) of the present disclosure, the bioprocess bag of any of aspects (9)-(12) is provided, wherein the metal port fitment comprises a plurality of fluid ports.

[0071] According to an aspect (14) of the present disclosure, the bioprocess bag of any of aspects (9)-(13) is provided, wherein the metal port fitment comprises a boat shaped port fitment.

[0072] According to an aspect (15) of the present disclosure, a bioprocess bag is provided. The bioprocess bag comprises: a film or laminate comprising a polymer layer; a metal contact layer; and a plastic port fitment comprising at least one fluid port, wherein the plastic port fitment is welded to the polymer layer to form a hermetically sealed interior compartment. [0073] According to an aspect (16) of the present disclosure, the bioprocess bag of aspect

(15) is provided, wherein the polymer layer is welded to an exterior surface of the plastic port fitment.

[0074] According to an aspect (17) of the present disclosure, the bioprocess bag of aspect

(15) is provided, wherein the polymer layer is welded to an interior surface of the plastic port fitment.

[0075] According to an aspect (18) of the present disclosure, the bioprocess bag of any of aspects (15)-(17) is provided, wherein the plastic port fitment comprises a polymer selected from the group consisting of high density polypropylene (HDPE), polypropylene, EVA, LDPE and LLDPE.

[0076] According to an aspect (19) of the present disclosure, the bioprocess bag of any of aspects (15)-(18) is provided, wherein the plastic port fitment comprises a plurality of fluid ports.

[0077] According to an aspect (20) of the present disclosure, the bioprocess bag of any of aspects (15)-(19) is provided, wherein the plastic port fitment comprises a boat shaped port fitment.

[0078] According to an aspect (21) of the present disclosure, the bioprocess bag of any of aspects (9)-(20) is provided, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

[0079] According to an aspect (22) of the present disclosure, the bioprocess bag of aspect

(21) is provided, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

[0080] According to an aspect (23) of the present disclosure, a bioprocess bag is provided. The bioprocess bag comprises: a film or laminate; a metal contact layer; at least one connection apparatus comprising at least one internal fluid passage; and at least one tube connected to the at least one connection apparatus and comprising a metal coating or laminate disposed on an interior wall of the at least one tube. [0081] According to an aspect (24) of the present disclosure, the bioprocess bag of aspect

(23) is provided, wherein the at least one tube comprises a polymer selected from the group consisting of polytetrafluoro ethylene (PTFE), polyvinylidene fluoride (PVDF), very low density polyethylene (VLDPE), ethylene vinyl acetate co-polymers (EVA) and combinations thereof.

[0082] According to an aspect (25) of the present disclosure, the bioprocess bag of any of aspects (23)-(24) is provided, wherein the metal coating or laminate comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[0083] According to an aspect (26) of the present disclosure, the bioprocess bag of any of aspects (23)-(25) is provided, wherein the at least one connection apparatus comprises a port fitment.

[0084] According to an aspect (27) of the present disclosure, the bioprocess bag of aspect

(26) is provided, wherein the port fitment comprises a metal port fitment.

[0085] According to an aspect (28) of the present disclosure, the bioprocess bag of aspect

(26) is provided, wherein the port fitment comprises a plastic port fitment.

[0086] According to an aspect (29) of the present disclosure, the bioprocess bag of aspect

(26) is provided, wherein the port fitment comprises a boat shaped port fitment.

[0087] According to an aspect (30) of the present disclosure, the bioprocess bag of any of aspects (23)-(25) is provided, wherein the at least one connection apparatus comprises a metallic connector.

[0088] According to an aspect (31) of the present disclosure, the bioprocess bag of aspect

(30) is provided, further comprising at least one metal foil comprising a fluid passage, wherein the metal foil contacts the metal contact layer and wherein the metal foil is connected to the film or laminate to form a hermetically sealed interior compartment.

[0089] According to an aspect (32) of the present disclosure, the bioprocess bag of aspect

(31) is provided, wherein the metallic connector comprises an internal fluid passage, wherein the metallic connector is connected to the metal foil and wherein the internal fluid passage of the metallic connector is fluidly connected to the fluid passage of the metal foil.

[0090] According to an aspect (33) of the present disclosure, the bioprocess bag of any of aspects (l)-(32) is provided, wherein the metal contact layer comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[0091] According to an aspect (34) of the present disclosure, the bioprocess bag of any of aspects (l)-(33) is provided, wherein the film or laminate comprises a polymer layer comprising a polymer selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephtalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), poly ether ether ketone (PEEK) polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA) and derivatives thereof.

[0092] According to an aspect (35) of the present disclosure, the bioprocess bag of any of aspects (l)-(34) is provided comprising at least two sheets of the film or laminate welded along the edges of the sheets to form a pillow-shaped bag.

[0093] According to an aspect (36) of the present disclosure, the bioprocess bag of any of aspects (l)-(34) is provided comprising a bottom portion, a top portion and a sidewall defining the interior compartment.

[0094] According to an aspect (37) of the present disclosure, a method of forming a bioprocess bag is provided. The method comprises: forming a bioprocess bag comprising a film or laminate and a metal contact layer, the bioprocess bag having at least one opening; inserting at least one metallic connector into the at least one opening such that the at least one metallic connector contacts the metal contact layer; and heating the film or laminate to form a heat seal around a portion of the at least one metal connector.

[0095] According to an aspect (28) of the present disclosure, the method of aspect (37) is provided, further comprising connecting a portion of the metallic connector to the metal contact layer. [0096] According to an aspect (29) of the present disclosure, the method of any of aspects (37)-(38) is provided, wherein the bioprocess bag comprises a plurality of metallic connectors.

[0097] According to an aspect (40) of the present disclosure, a method of forming a bioprocess bag is provided. The method comprises: forming a bioprocess bag comprising a film or laminate and a metal contact layer, the bioprocess bag having at least one opening; inserting a first end of at least one metal foil into the at least one opening such that the first end contacts the metal contact layer, the at least one metal foil comprising a fluid passage; connecting a second end of the at least one metal foil to a metallic connector comprising an internal fluid passage, wherein connecting the second end of the at least one metal foil to a metallic connector fluidly connects the fluid passage of the at least one metal foil to the internal fluid passage of the at least one metallic connector; and connecting the metal foil to the film or laminate to seal the at least one opening.

[0098] According to an aspect (41) of the present disclosure, the method of aspect (40) is provided, wherein the metal foil comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[0099] According to an aspect (42) of the present disclosure, the method of any of aspects (40)-(41) is provided, wherein the bioprocess bag comprises a plurality of metal foils and a plurality of metallic connectors.

[00100] According to an aspect (43) of the present disclosure, the method of any of aspects (37)-(42) is provided, wherein the metallic connector comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[00101] According to an aspect (44) of the present disclosure, a method of forming a bioprocess bag is provided. The method comprises: forming a bioprocessing bag comprising a film or laminate and a metal contact layer, the bioprocessing bag having an opening; inserting a metal port fitment into the opening; heating the film or laminate; and welding the metal contact layer to the metal port fitment to form a hermetically sealed interior compartment.

[00102] According to an aspect (45) of the present disclosure, the method of aspect (44) is provided, wherein welding the metal contact layer to the metal port fitment comprises welding the metal contact layer to an exterior surface of the metal port fitment.

[00103] According to an aspect (46) of the present disclosure, the method of aspect (44) is provided, wherein welding the metal contact layer to the metal port fitment comprises welding the metal contact layer to an interior surface of the metal port fitment.

[00104] According to an aspect (47) of the present disclosure, the method of any of aspects (44)-(46) is provided, wherein the metal port fitment comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[00105] According to an aspect (48) of the present disclosure, the method of any of aspects (44)-(47) is provided, wherein the metal port fitment comprises at least one fluid port.

[00106] According to an aspect (49) of the present disclosure, the method of aspect (48) is provided, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

[00107] According to an aspect (50) of the present disclosure, the method of aspect (49) is provided, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

[00108] According to an aspect (51) of the present disclosure, the method of any of aspects (44)-(50) is provided, wherein the metal port fitment comprises a boat shaped port fitment.

[00109] According to an aspect (52) of the present disclosure, a method of forming a bioprocess bag is provided. The method comprises: forming a bioprocessing bag comprising a film or laminate comprising a polymer layer, the bioprocessing bag further comprising a metal contact layer and having an opening; inserting a plastic port fitment into the opening; heating the film or laminate; and welding the polymer layer to the plastic port fitment to form a hermetically sealed interior compartment.

[00110] According to an aspect (53) of the present disclosure, the method of aspect (52) is provided, wherein welding the polymer layer to the plastic port fitment comprises welding the polymer layer to an exterior surface of the plastic port fitment.

[00111] According to an aspect (54) of the present disclosure, the method of aspect (52) is provided, wherein welding the polymer layer to the plastic port fitment comprises welding the polymer layer to an interior surface of the plastic port fitment.

[00112] According to an aspect (55) of the present disclosure, the method of any of aspects (52)-(54) is provided, wherein the plastic port fitment comprises a polymer selected from the group consisting of high density polypropylene (HDPE), polypropylene, EVA, LDPE and LLDPE.

[00113] According to an aspect (56) of the present disclosure, the method of any of aspects (52)-(55) is provided, wherein the plastic port fitment comprises at least one fluid port.

[00114] According to an aspect (57) of the present disclosure, the method of aspect (56) is provided, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

[00115] According to an aspect (58) of the present disclosure, the method of aspect (56) is provided, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

[00116] According to an aspect (59) of the present disclosure, the method of any of aspects (52)-(58) is provided, wherein the plastic port fitment comprises a boat shaped port fitment. [00117] According to an aspect (60) of the present disclosure, the method of any of aspects (52)-(59) is provided, further comprising metallizing a portion of an interior surface of the plastic port fitment.

[00118] According to an aspect (61) of the present disclosure, the method of aspect (60) is provided, wherein metallizing a portion of an interior surface of the plastic port fitment comprises metallizing vacuum metallizing, arc spraying, flame spraying, electroless plating or electroplating a portion of an interior surface of the plastic port fitment.

[00119] According to an aspect (62) of the present disclosure, the method of aspect (60) is provided, wherein a portion the interior surface of the plastic port fitment is at least one of the interior surface of the plastic port fitment, the interior surface of an at least one fluid port and the interior surface of an extension having an interior passage fluid communication with the at least one fluid port.

[00120] According to an aspect (63) of the present disclosure, the method of any of aspects (37)-(62) is provided, wherein the metal contact layer comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

[00121] According to an aspect (64) of the present disclosure, the method of any of aspects (37)-(63) is provided, wherein the film or laminate comprises a polymer layer comprising a polymer selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephtalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), poly ether ether ketone (PEEK) polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA) and derivatives thereof.

[00122] According to an aspect (65) of the present disclosure, the method of any of aspects (37)-(64) is provided, wherein forming a bioprocess bag comprises welding at least two sheets of the film or laminate along the edges of the sheets to form a pillow-shaped bag. [00123] According to an aspect (66) of the present disclosure, the method of any of aspects (37)-(64) is provided, wherein forming a bioprocess bag comprises forming a bioprocess bag having a bottom portion, a top portion and a sidewall defining the interior compartment.

[00124] While the present disclosure includes a limited number of embodiments, those skilled in the art, having benefit of this disclosure, will appreciate that other embodiments can be devised which do not depart from the scope of the present disclosure.

Claims

CLAIMS What Is Claimed Is:

1. A bioprocess bag comprising: a film or laminate; a metal contact layer; and a metallic connector comprising an internal fluid passage, wherein the metallic connector contacts the metal contact layer, and wherein the film or laminate is heat sealed around a portion of the metallic connector to form a hermetically sealed interior compartment.

2. The bioprocess bag of claim 1, wherein a portion of the metallic connector is connected to the metal contact layer.

3. The bioprocess bag of any of the preceding claims comprising a plurality of metallic connectors.

4. A bioprocess bag comprising: a film or laminate; a metal contact layer; at least one metal foil comprising a fluid passage, wherein the metal foil contacts the metal contact layer and wherein the metal foil is connected to the film or laminate to form a hermetically sealed interior compartment; and at least one metallic connector comprising an internal fluid passage, wherein the metallic connector is connected to the metal foil and wherein the internal fluid passage of the metallic connector is fluidly connected to the fluid passage of the metal foil.

5. The bioprocess bag of claim 4 further comprising an adhesive which connects the metal foil to the portion of the metallic connector.

6. The bioprocess bag of any of claims 4-5 further comprising an adhesive which connects the metal foil to the film or laminate.

7. The bioprocess bag of any of claims 4-6 comprising a plurality of metal foils and a plurality of metallic connectors.

8. The bioprocess bag of any of the preceding claims, wherein the metallic connector comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

9. A bioprocessing bag comprising: a film or laminate; a metal contact layer; and a metal port fitment comprising at least one fluid port, wherein the metal port fitment is welded to the metal contact layer to form a hermetically sealed interior compartment.

10. The bioprocessing bag of claim 9, wherein the metal contact layer is welded to an exterior surface of the metal port fitment.

11. The bioprocess bag of any of claims 9, wherein the metal contact layer is welded to an interior surface of the metal port fitment.

12. The bioprocess bag of any of claims 9-11, wherein the metal port fitment comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

13. The bioprocess bag of any of claims 9-12, wherein the metal port fitment comprises a plurality of fluid ports.

14. The bioprocess bag of any of claims 9-13, wherein the metal port fitment comprises a boat shaped port fitment.

15. A bioprocessing bag comprising: a film or laminate comprising a polymer layer; a metal contact layer; and a plastic port fitment comprising at least one fluid port, wherein the plastic port fitment is welded to the polymer layer to form a hermetically sealed interior compartment.

16. The bioprocessing bag of claim 15, wherein the polymer layer is welded to an exterior surface of the plastic port fitment.

17. The bioprocess bag of any of claims 15, wherein the polymer layer is welded to an interior surface of the plastic port fitment.

18. The bioprocess bag of any of claims 15-17, wherein the plastic port fitment comprises a polymer selected from the group consisting of high density polypropylene (HDPE),

polypropylene, EVA, LDPE and LLDPE.

19. The bioprocess bag of any of claims 15-18, wherein the plastic port fitment comprises a plurality of fluid ports.

20. The bioprocess bag of any of claims 15-19, wherein the plastic port fitment comprises a boat shaped port fitment.

21. The bioprocessing bag of any of claims 9-20, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

22. The bioprocessing bag of claim 21, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

23. A bioprocess bag comprising: a film or laminate; a metal contact layer; at least one connection apparatus comprising at least one internal fluid passage; and at least one tube connected to the at least one connection apparatus and comprising a metal coating or laminate disposed on an interior wall of the at least one tube.

24. The bioprocess bag of claim 23, wherein the at least one tube comprises a polymer selected from the group consisting of polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), very low density polyethylene (VLDPE), ethylene vinyl acetate co-polymers (EVA) and combinations thereof.

25. The bioprocess bag of any of claims 23-24, wherein the metal coating or laminate comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

26. The bioprocess bag of any of claims 23-25, wherein the at least one connection apparatus comprises a port fitment.

27. The bioprocess bag of claim 26, wherein the port fitment comprises a metal port fitment.

28. The bioprocess bag of claim 26, wherein the port fitment comprises a plastic port fitment.

29. The bioprocess bag of claim 26, wherein the port fitment comprises a boat shaped port fitment.

30. The bioprocess bag of any of claims 23-25, wherein the at least one connection apparatus comprises a metallic connector.

31. The bioprocess bag of claim 30, further comprising at least one metal foil comprising a fluid passage, wherein the metal foil contacts the metal contact layer and wherein the metal foil is connected to the film or laminate to form a hermetically sealed interior compartment.

32. The bioprocess bag of claim 31, wherein the metallic connector comprises an internal fluid passage, wherein the metallic connector is connected to the metal foil and wherein the internal fluid passage of the metallic connector is fluidly connected to the fluid passage of the metal foil.

33. The bioprocess bag of any of the preceding claims, wherein the metal contact layer comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

34. The bioprocess bag of any of the preceding claims, wherein the film or laminate comprises a polymer layer comprising a polymer selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephtalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), poly ether ether ketone (PEEK) polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA) and derivatives thereof.

35. The bioprocess bag of any of the preceding claims comprising at least two sheets of the film or laminate welded along the edges of the sheets to form a pillow-shaped bag.

36. The bioprocess bag of any of claims 1-34 comprising a bottom portion, a top portion and a sidewall defining the interior compartment.

37. A method of forming a bioprocess bag, the method comprising: forming a bioprocess bag comprising a film or laminate and a metal contact layer, the bioprocess bag having at least one opening; inserting at least one metallic connector into the at least one opening such that the at least one metallic connector contacts the metal contact layer; and heating the film or laminate to form a heat seal around a portion of the at least one metal connector.

38. The method of claim 37, further comprising connecting a portion of the metallic connector to the metal contact layer.

39. The method of any of claims 37-38, wherein the bioprocess bag comprises a plurality of metallic connectors.

40. A method of forming a bioprocess bag, the method comprising: forming a bioprocess bag comprising a film or laminate and a metal contact layer, the bioprocess bag having at least one opening; inserting a first end of at least one metal foil into the at least one opening such that the first end contacts the metal contact layer, the at least one metal foil comprising a fluid passage; connecting a second end of the at least one metal foil to a metallic connector comprising an internal fluid passage, wherein connecting the second end of the at least one metal foil to a metallic connector fluidly connects the fluid passage of the at least one metal foil to the internal fluid passage of the at least one metallic connector; and connecting the metal foil to the film or laminate to seal the at least one opening.

41. The method of claim 40, wherein the metal foil comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

42. The method of any of claims 40-41, wherein the bioprocess bag comprises a plurality of metal foils and a plurality of metallic connectors.

43. The method of any of claims 37-42, wherein the metallic connector comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

44. A method of forming a bioprocess bag, the method comprising: forming a bioprocessing bag comprising a film or laminate and a metal contact layer, the bioprocessing bag having an opening; inserting a metal port fitment into the opening; heating the film or laminate; and welding the metal contact layer to the metal port fitment to form a hermetically sealed interior compartment.

45. The method of claim 44, wherein welding the metal contact layer to the metal port fitment comprises welding the metal contact layer to an exterior surface of the metal port fitment.

46. The method of claim 44, wherein welding the metal contact layer to the metal port fitment comprises welding the metal contact layer to an interior surface of the metal port fitment.

47. The method of any of claims 44-46, wherein the metal port fitment comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

48. The method of any of claims 44-47, wherein the metal port fitment comprises at least one fluid port.

49. The method of claim 48, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

50. The method of claim 49, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

51. The method of any of claims 44-50, wherein the metal port fitment comprises a boat shaped port fitment.

52. A method of forming a bioprocess bag, the method comprising: forming a bioprocessing bag comprising a film or laminate comprising a polymer layer, the bioprocessing bag further comprising a metal contact layer and having an opening; inserting a plastic port fitment into the opening; heating the film or laminate; and welding the polymer layer to the plastic port fitment to form a hermetically sealed interior compartment.

53. The method of claim 52, wherein welding the polymer layer to the plastic port fitment comprises welding the polymer layer to an exterior surface of the plastic port fitment.

54. The method of claim 52, wherein welding the polymer layer to the plastic port fitment comprises welding the polymer layer to an interior surface of the plastic port fitment.

55. The method of any of claims 52-54, wherein the plastic port fitment comprises a polymer selected from the group consisting of high density polypropylene (HDPE), polypropylene, EVA, LDPE and LLDPE.

56. The method of any of claims 52-55, wherein the plastic port fitment comprises at least one fluid port.

57. The method of claim 56, wherein the at least one fluid port is in fluid communication with an interior passage of an extension.

58. The method of claim 56, wherein the extension comprises a coupler configured to engage an open end of a length of tubing.

59. The method of any of claims 52-58, wherein the plastic port fitment comprises a boat shaped port fitment.

60. The method of any of claims 52-59, further comprising metallizing a portion of an interior surface of the plastic port fitment.

61. The method of claim 60, wherein metallizing a portion of an interior surface of the plastic port fitment comprises metallizing vacuum metallizing, arc spraying, flame spraying, electroless plating or electroplating a portion of an interior surface of the plastic port fitment.

62. The method of claim 60, wherein a portion the interior surface of the plastic port fitment is at least one of the interior surface of the plastic port fitment, the interior surface of an at least one fluid port and the interior surface of an extension having an interior passage fluid communication with the at least one fluid port.

63. The method of any of claims 37-62, wherein the metal contact layer comprises a metal selected from the group consisting of stainless steel, nickel, chromium, titanium, molybdenum, tungsten, tantalum, niobium, zirconium, gold, tin, and oxides and alloys thereof.

64. The method of any of claims 37-63, wherein the film or laminate comprises a polymer layer comprising a polymer selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephtalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), polyetheretherketone (PEEK)

polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA) and derivatives thereof.

65. The method of any of claims 37-64, wherein forming a bioprocess bag comprises welding at least two sheets of the film or laminate along the edges of the sheets to form a pillow- shaped bag.

66. The method of any of claims 37-64, wherein forming a bioprocess bag comprises forming a bioprocess bag having a bottom portion, a top portion and a sidewall defining the interior compartment.