Patent Description:
Chemical, biological, and biopharmaceutical manufacturing facilities have traditionally employed the use of large stainless-steel vats in their manufacturing processes. Due to the expense of these systems, including the costs involved in cleaning and sterilizing vats between production batches, manufacturers are increasingly moving toward single-use systems for holding chemical or biological media during processing, storage, and/or transport of the media. <CIT> describes medical containers which are made of a multi-layered film including a polyolefin and which can be sterilised by autoclave. <CIT> describes a sterile disposable bag with an interior surface made of melt-fabricable fluoropolymer.

The present disclosure relates generally to robust bag assemblies that are capable of withstanding sterilization by gamma irradiation, and securely retaining a chemical, biological, and biopharmaceutical media, while also allowing for easy access to the interior of the bag assemblies for the filling and extraction of the media from the bag assembly.

According to various embodiments, a bag assembly capable of withstanding sterilization by gamma irradiation includes a bag portion and a fitment. The bag assembly can also include at least one fitting extending from the fitment, wherein the at least one fitting is in communication through the fitment to the interior of the bag portion. The bag assembly can be a stand-alone article or can be contained within an outer container. In many cases, the bag assembly is capable of withstanding an amount of gamma radiation of: at least <NUM> kGy of gamma radiation up to about <NUM> kGy of gamma radiation, to at least <NUM> kGy of gamma radiation up to about <NUM> kGy of gamma radiation, at least <NUM> kGy of gamma radiation up to about <NUM> kGy of gamma radiation; or at least <NUM> kGy of gamma radiation up to about <NUM> kGy of gamma radiation. In addition to its ability to withstand sterilization by gamma irradiation, the bag assembly, in certain embodiments, may withstand temperatures of -<NUM> degrees C or even lower as determined by ISO <NUM> cold crack test. Some of the disclosed bag assemblies have a water vapor permeability of less than <NUM>/m2. Others are UV stable. Some of the disclosed bag assembly may be desirably formed without the use of adhesives, solvents, or binders.

The bag portion of the bag assembly includes first and second walls, wherein each of the first and second walls composed of at least one sheet of a fluoropolymer film. The fluoropolymer film from which the bag portion is formed can be a single layer film. The fitment includes first and second sidewalls extending between opposing end points, and can also be composed of a fluoropolymer. A portion of each of the first and second walls of the bag portion are attached to each other along at least a portion of a perimeter of the bag assembly up to the opposing end points of the fitment defining an interior of the bag portion. In some embodiments, the first and second walls can be continuously bonded along a majority of the perimeter of the bag assembly. In addition, each of the first and second walls are bonded individually to one of the first and second sidewalls of the fitment.

In some embodiments, at least one of the first and second sidewalls of the fitment has a curved portion extending between the opposing end points. In other embodiments, each of the first and second sidewalls of the fitment have curved portions extending between the opposing end points. The fitment comprises the same fluoropolymer as the fluoropolymer film used to form the first and second walls of the bag portion. The utilization of similar fluoropolymers may enhance the attachment between the first and second walls of the bag portion to the sidewalls of the fitment. One or more of the first and second walls of the bag portion, the fitment or the at least one fitting can be composed of an ethylenetetrafluoroethylene polymer, a polychlorotrifluoroethylene polymer, a polyvinyl fluoride polymer, a polyvinylidene fluoride polymer, or a combination thereof. In some embodiments, the fluoropolymer is an ethylenetetrafluoroethylene polymer. In another embodiment, the fluoropolymer film may be in the form of a single layer film.

The preceding summary is provided to facilitate an understanding of some of the innovative features unique to the present disclosure and is not intended to be a full description. A full appreciation of the disclosure can be gained by taking the entire specification, claims, drawings, and abstract as a whole.

The disclosure may be more completely understood in consideration of the following description of various illustrative embodiments in connection with the accompanying drawings.

It should be understood, however, that the intention is not to limit aspects of the disclosure to the particular illustrative embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure.

As used herein, the term "about" refers to a range of numbers that is considered equivalent to the recited value (e.g., having the same function or result).

As used herein, the term "attached" is generally used to refer two or more structures that are joined, fastened or otherwise connected to one another. In some cases, the term "attached" is used herein to refer to two or more structures that have been bonded or welded together. More particularly, the term "attached" is used herein to refer to two or more structures that have been bonded or welded together without the use of adhesives, solvents or binders.

As used herein, the term "gamma radiation" is defined as penetrating electromagnetic radiation of a kind arising from the radioactive decay of atomic nuclei. Gamma radiation is composed of photons in the highest observed range of photon energy. The effect of gamma radiation on a material is more closely related to the amount of energy deposited rather than the charge, and is referred to as the absorbed dose. The gray (Gy), which has units of joules per kilogram (J/kg), is the SI unit of absorbed dose, and is the amount of radiation required to deposit <NUM> joule of energy in <NUM> kilogram of any kind of matter.

As used herein, the terms "gamma sterilization" or "gamma irradiation" refers to the use of gamma radiation to sterilize an article. Gamma sterilization or gamma irradiation uses Cobalt <NUM> to kill microorganisms on a variety of different products. The radioisotope Cobalt <NUM> is the energy source for use in gamma irradiation with the irradiation process taking place in a specially designed cell. A characteristic of gamma irradiation is its high penetration capability.

As used herein, the term "capable of withstanding sterilization by gamma irradiation" is used to refer to a material that does not substantially degrade, physically or chemically, when exposed to gamma radiation.

As used herein, the term "materially stable" refers to a material or assembly that substantially maintains its mechanical and chemical integrity when subjected to gamma radiation.

As used herein, the terms "UV stable" or "UV stability" is used to describe a material that does not substantially degrade when exposed to ultraviolet radiation.

As used herein, the term "single-use" encompasses a broad range of primarily plastic disposable technologies that are suitable for a wide variety of scales and applications, from upscale bioprocessing to final formulation and filling.

As used herein, the term "fitment" refers to a structure that provides communication with the interior of a bag assembly and that facilitates the introduction of media or the removal of media from the interior of the bag assembly.

As used herein, the term "fitting" refers to a structure that is connectable to the fitment, and which also provides communication with the interior of the bag assembly. A fitting typically includes additional structural features which facilitates a connection between different structures. Exemplary fittings include, but are not limited to hose barbs, Luer fittings, quick connectors, such as Primelock® (Entegris, Billerica, MA) and Quikgrip® fittings (Entegris, Billerica, MA), and flare-type fittings, such as Flaretek® fittings (Entegris, Billerica, MA).

As used herein, the term "two-dimensional bag assembly" refers to a bag assembly having a bag portion in which one or more sheets of a polymer film are welded or bonded together at their edges to form a generally flat, pillow-like enclosure defining an interior.

As used herein, the term "outer container" is used to refer to a first container in which is disposed a second container such as, for example, a bag assembly as described herein. In some cases, the outer container can be rigid and can protect the inner container or bag assembly, but this is not required.

As used herein, the term "single layer" refers to a sheet having a single layer of a polymer material and excludes any intervening layers such as barrier layers, adhesive layers tie layers, or combinations thereof.

As used herein, the term "polymer" refers to substance that has a molecular structure consisting chiefly or entirely of a large number of similar units, called monomer units, bonded together.

As used herein, the term "homopolymer" refers to a polymer which consists of repeating, identical monomer units.

As used herein, the term "copolymer" refers to a polymer made by reaction of two different monomers, with units of more than one kind.

Chemical, biological, and biopharmaceutical materials often require storage in vessels, such as polymeric containers, that are intended to offer a stable and sterile environment. However, such storage vessels may undesirably contaminate the material contained in the vessel by leaching chemicals or other extractables from the materials forming the vessel or through contaminants remaining in the vessel. Additionally, attempts to sterilize certain vessels may adversely affect the materials of construction and degrade those materials. The unwanted degradation can possibly introduce new contaminants and severely limit the service life or potential application of the vessel.

The bag assemblies, as described herein according to the various embodiments, overcome some of the challenges of currently available bag assemblies by providing a product that possesses one or more desirable characteristics such as for example a high purity; chemically compatible with a variety of media; able to be used in cold storage and more particularly, cryogenic applications; and is materially stable when sterilized. Sterilization may be accomplished by exposing the bag assembly to gamma rays. Without being bound by theory, it is believed gamma irradiation is capable of killing bacteria by breaking the covalent bonds of bacterial DNA. Gamma irradiation can be one effective form of sterilization and advantageous because gamma irradiation is not a heat-generating process. Heat generated during certain sterilization practices can stress the bag assembly and could compromise the stability and durability of the completed article. Gamma irradiation also does not involve the use of moisture and, as such, does not require drainage of condensation or outgassing following sterilization. Additionally, in some embodiments, following gamma irradiation, there is substantially no residual radioactivity detected from the bag.

According to various embodiments, the disclosed bag assembly can be constructed from a fluoropolymer film that is selected for a combination of chemical and physical properties. Non-limiting properties of the fluoropolymer film may include the ability to withstand sterilization by gamma irradiation; processability at high shear rates; low water vapor permeability; chemical compatibility with a wide range of materials; UV stability; and the ability to withstand temperatures of -<NUM>, possibly -<NUM>, or possibly lower. In certain embodiments, the bag assembly is capable of withstanding up to of at least <NUM> kGy and up to about <NUM> kGy, <NUM> kGy, <NUM> kGy, or <NUM> kGy of gamma radiation.

The bag portion of the bag assembly is generally constructed of a fluoropolymer film. In some embodiments, the fluoropolymer film includes an ethylenetetrafluoroethylene (ETFE) polymer, a polychlorotrifluoroethylene (PCTFE) polymer, a polyvinyl fluoride (PVF) polymer, a polyvinylidene fluoride (PVDF) polymer or a combination thereof. In another embodiment, the fluoropolymer film includes an ethylenetetrafluoroethylene (ETFE) polymer, a polyvinyl fluoride (PVF) polymer, a polyvinylidene fluoride (PVDF) polymer or a combination thereof. In still another embodiment, ETFE may be particularly suited for construction of the bag assemblies. In accordance with this disclosure, certain fluoropolymer films may desirably possess one or more of (i) the ability to withstanding sterilization by gamma irradiation, (ii) may be processed at high shear rates, (iii) are melt processable for example by injection-molding, (iv) possess chemically stability in the presence of a wide range of materials, (v) withstand cold temperatures including those as low as -<NUM>° C and more particularly, as low as -<NUM> when subjected to cold crack testing as specified by ISO <NUM>: <NUM> (E), (vi) have a water vapor permeability of <NUM>/m<NUM>. bar, and is UV stable.

Turning now to the drawings, <FIG> show an exemplary bag assembly <NUM>. As best seen in <FIG> and <FIG>, the bag assembly <NUM> includes a bag portion <NUM> and a fitment <NUM>. In some cases, the first and second walls <NUM>, <NUM> are welded or bonded together at their respective edges along a majority of the perimeter <NUM> of the bag assembly <NUM> up to the opposing ends <NUM>, <NUM> of the fitment <NUM> (<FIG>) to define the interior of the bag portion <NUM>. The bond or weld formed between the first and second walls <NUM>, <NUM> can be a continuous bond or weld about a majority of the perimeter <NUM> of the bag assembly <NUM> up to the opposing ends <NUM>, <NUM> of the fitment <NUM>. Any suitable welding or bonding technique known to those of skill in the art may be used to attach the first and second walls <NUM>, <NUM> of the bag portion together at their respective edges <NUM>, <NUM>, <NUM>, <NUM> and <NUM>. Exemplary welding or bonding techniques can include, but are not limited to heat bonding, impulse welding, laser welding, ultrasonic welding, platen welding, or the like. However, in many cases, the first and second walls <NUM>, <NUM> of the bag portion <NUM> are attached to each other at their respective edges without the use of adhesives, solvents or binders. Eliminating the use of adhesives, solvents or solvents in the construction of the bag assembly <NUM> can enhance the overall purity of the final assembly as the number of sources of potential leachable and extractables are reduced.

In some embodiments, as shown in <FIG>, the bag portion <NUM> includes first and second walls <NUM>, <NUM>, a top edge <NUM>, two side edges <NUM> and <NUM>, two angled side edges <NUM> and <NUM>, and a bottom edge <NUM>. The first and second walls <NUM>, <NUM> can be attached to each other at the respective edges <NUM>, <NUM>, <NUM>, <NUM> and <NUM> of the bag portion <NUM> to form a seam <NUM> along at least a portion of the perimeter <NUM> of the bag assembly <NUM> to define an interior of the bag portion <NUM>. As depicted in <FIG>, seam <NUM> of bag assembly <NUM> can have varying seam widths along the perimeter of the bag. The width of seam <NUM> can provide a sufficient weld width or weld thickness for structural durability as well as providing expanded areas to accommodate additional features, such as opening <NUM> through which a hook or other fixture can be threaded such that the bag assembly <NUM> can be suspended. For example, the seam <NUM> can be formed to have a weld width WA along top edge <NUM>, weld width WB along bottom edge <NUM>, and weld width WC around side and angled edges <NUM>, <NUM>, <NUM>, <NUM>. Weld width WB can be made to accommodate the size of fitment <NUM>, and to provide a sufficiently large weld width to effectively bond films <NUM>, <NUM> to the fitment <NUM>. Weld width WC can be at least a minimum weld width to provide an effective seal along seam <NUM>. Weld width WA can be made wider to provide additional area for opening <NUM>. In addition, the angled side edges <NUM>, <NUM> can reduce stress concentrations that are typically formed with sharp corners. The angled side edges <NUM>, <NUM>, as opposed to right-angled edges near bottom edge <NUM>, can provide a more balanced distribution of weight of media contained in the bag assembly <NUM>, decreasing strain on seam <NUM> along edges at or near the bottom of the bag.

In some embodiments, the first and second walls <NUM>, <NUM> are heat bonded to each other and to the fitment over a weld width, or weld thickness, of about <NUM>/<NUM> inch (about <NUM>) to about <NUM>/<NUM> inch (about <NUM>). In a particular embodiment, the first and second walls are heat bonded to each other and to the fitment over a weld width of about <NUM>/<NUM> inch (about <NUM>). A separate weld can be used along edge <NUM>, with this weld being a different width than the weld provided around edges <NUM>, <NUM>, <NUM>-<NUM>. This is shown in <FIG>, for example, where unsealed areas <NUM>, <NUM> are located between the welds at two corners of bag assembly <NUM>.

Each of the first and second walls <NUM>, <NUM> of the bag portion <NUM> can be formed from at least one sheet of a fluoropolymer film. In certain aspects, the first and second walls <NUM>, <NUM> of the bag portion <NUM> are formed from a single sheet of a fluoropolymer film. The single sheet of fluoropolymer film excludes any intervening layers such as barrier layers, adhesive layers tie layers or combinations thereof. Use of a single sheet of a fluoropolymer film having no intervening layers reduces the potential number of sources of leachables or extractables, and may enhance the overall purity of the final assembly.

In one embodiment, each sheet of fluoropolymer forming the walls <NUM>, <NUM> of the bag portion <NUM> of the bag assembly <NUM> can have a thickness of about <NUM> mil (<NUM> p. m) to about <NUM> mil (<NUM> p. m), or of about <NUM> mil (<NUM> p. m) to about <NUM> mil (<NUM> p. In one embodiment, each sheet of fluoropolymer film forming the walls lof a bag assembly has a thickness of about <NUM> mil (<NUM> p.

As best viewed in <FIG>, the first and second walls <NUM>, <NUM> of the body portion <NUM> are attached to the fitment <NUM> to form the bag assembly <NUM>. The fitment <NUM> forming a part of the bag assembly <NUM> can be any suitable structure that provides communication with the interior of a bag assembly, and that facilitates the introduction or removal of a fluid or other substance such as, for example, a powdered material, from the interior of a bag assembly such as, bag assembly <NUM>. As shown in <FIG>, the fitment <NUM> includes a first side wall <NUM> and a second side wall <NUM> extending between two opposing end points <NUM>, <NUM>. At least one of the first and second side walls <NUM>, <NUM> can be curved. In some cases, both of the first and second side walls <NUM>, <NUM> are curved between the opposing end points <NUM>, <NUM> of the fitment. More particularly, both of the first and second side walls <NUM>, <NUM> of the fitment can be curved such that the first and second side walls <NUM>, <NUM> are symmetrical about a longitudinal axis of the fitment <NUM>.

A portion of the first wall <NUM> is attached to a first side wall <NUM> of the fitment <NUM> and a portion of the second wall <NUM> of the bag portion <NUM> is attached to the second side wall of the fitment <NUM> thus placing the fitment <NUM> in communication with the interior of the bag portion <NUM>. The first and second walls <NUM> of the bag portion <NUM> can be welded or bonded to the first and second side walls <NUM>, <NUM> such that a continuous bond or weld is formed about the entire perimeter <NUM> of the bag assembly <NUM>. In some cases, as can be seen in <FIG>, the first and second walls <NUM>, <NUM> of the bag portion <NUM> are attached to first and second sidewalls <NUM>, <NUM> of the fitment such that the walls follow the contour of the walls <NUM>, <NUM> of the fitment <NUM>. The contoured shape of the fitment <NUM> provides a continuous surface for the attachment of each of the first and second walls <NUM>, <NUM> of the bag portion <NUM> to the respective sidewalls <NUM>, <NUM> of the fitment <NUM>. The attachment of the first and second walls <NUM>, <NUM> along a continuous surface may remove any points of weakness that would occur if, for example, the walls were bonded to a fitment having sharper angled edges or to a fitment with a more circular shape, and may result in a more robust attachment between the bag portion <NUM> and the fitment <NUM>. Any suitable bonding or welding technique can be used to attach the first and second walls <NUM>, <NUM> of the bag portion <NUM> to the first and second sidewalls <NUM>, <NUM> of the fitment <NUM>. For example, the first and second walls <NUM>, <NUM> of the bag portion <NUM> may be attached to the side walls <NUM>, <NUM> of the fitment using heat boding, laser welding, ultrasonic welding, or platen welding techniques. In many embodiments, the attachment between the walls <NUM>, <NUM> of the bag portion <NUM> and the side walls <NUM>, <NUM> of the fitment <NUM> is made without the use of adhesives, solvents or binders, which can reduce the potential for leachables and extractables in the final bag assembly <NUM>. In some embodiments, the same attachment method used to attach the edges of the first and second walls <NUM> together can be used to attach a portion of the first and second walls <NUM>, <NUM> to the first and second side walls <NUM>, <NUM> of the fitment <NUM>.

The fitment <NUM> is shown in further detail in <FIG>. In some embodiments, as best seen in <FIG>, the side walls <NUM>, <NUM> of the fitment <NUM> are generally tapered from a convex region A, forming a central portion of the fitment <NUM>, to slightly concave regions B1 and B2 located at either end of the fitment. The strength of an attachment formed between walls <NUM>, <NUM> of the bag portion and the side walls <NUM>, <NUM> (when the fitment is installed as part of a bag assembly) can be positively correlated with the radius of curvature of the surface of the fitment <NUM>. The geometric shape of the sidewalls <NUM>, <NUM> maximizes the bend radius and eliminates discontinuities, permitting a smooth seal to be formed with each of the respective the bottom edges <NUM> of the first and second walls <NUM>, <NUM> of the bag portion <NUM> when the fitment <NUM> is installed as part of bag assembly <NUM>. Those of ordinary skill in the art will recognize that the fitment may possess various shapes and dimensions that enable bonding of the fluoropolymer film to the fitment to form the disclosed bag assembly. For example, in some embodiments, the fitment <NUM> can be a boat-shaped fitment. Boat-shaped fitments are also referred to as cat's eye fitments and diamond-shaped fitments.

Like the walls <NUM>, <NUM> of the bag portion <NUM>, the fitment <NUM> also can be formed from a fluoropolymer. In some aspects the fluoropolymer is a melt processable polymer that may enable formation of the fitment using conventional molding techniques such as injection molding. The fitment <NUM> comprises the same fluoropolymer as the first and second walls <NUM>, <NUM>. The criteria for selecting the fluoropolymer used to form the fitment <NUM> may be the same criteria as that used to select the fluoropolymer film used to form the walls of the bag portion. The fluoropolymer from which the fitment <NUM> can be formed is selected for a combination of chemical and physical properties. The fitment may desirably possess one or more of (i) the ability to withstanding sterilization by gamma irradiation, (ii) may be processed at high shear rates, (iii) are melt processable for example by injection-molding, (iv) possess chemically stability in the presence of a wide range of materials, (v) withstand cold temperatures including those as low as -<NUM>° C and more particularly, as low as -<NUM> when subjected to cold crack testing as specified by ISO <NUM>: <NUM> (E), (vi) have a water vapor permeability of <NUM>/m<NUM>. bar and is UV stable.

In some embodiments, the fluoropolymer used to form the fitment <NUM> includes an ethylenetetrafluoroethylene (ETFE) polymer, a polychlorotrifluoroethylene (PCTFE) polymer, a polyvinyl fluoride (PVF) polymer, a polyvinylidene fluoride (PVDF) polymer or a combination of these. In another embodiment, the fluoropolymer includes an ethylenetetrafluoroethylene (ETFE) polymer, a polyvinyl fluoride (PVF) polymer, a polyvinylidene fluoride (PVDF) polymer or a combination of these. In still another embodiment, ETFE is particularly suited for construction of the fitment for similar reasons as disclosed above for the fluoropolymer film.

The fitment <NUM> may be configured with one or more fittings <NUM>, <NUM> to enable ready and reliable connection with various parts and objects, such as tubing, connectors, hoses, syringes or the like. In various embodiments, the fitment <NUM> includes at least one fitting <NUM>, <NUM> that extend from the fitment <NUM>, and is in communication through the fitment <NUM> to the interior defined by the walls of the bag portion <NUM>. The fitting(s) <NUM>, <NUM> facilitates connection of various hoses, tubing, connectors, syringes or the like to the bag assembly <NUM>. Exemplary fittings include fittings include, but are not limited to, hose barbs, Luer fittings, quick connectors, such as Primelock® (Entegris, Billerica, MA) and Quikgrip® fittings (Entegris, Billerica, MA), and flare-type fittings, such as Flaretek® fittings (Entegris, Billerica, MA).

In some embodiments, as shown in <FIG>, the fitment <NUM> includes an opening <NUM>, placing three fittings, hose barbs <NUM> and <NUM>, in fluid communication with the interior of a bag assembly when the fitment <NUM> is included as part of the bag assembly <NUM>. The fitment <NUM> and opening <NUM> can be sized to accommodate communication between the bag interior and a variable number of fittings, including fittings, such as the hose barbs shown <NUM> and <NUM> shown in <FIG> and <FIG>. The various fittings <NUM> or <NUM> may be of the same size of different sizes. As illustrated, the fitment <NUM> includes three hose barbs, including one of a small barb <NUM> and two of a large barb <NUM>, although other configurations are possible. In some embodiments, one of the two large barbs <NUM> can function as an inlet, the other of the two large barbs <NUM> can function as an outlet, and the small barb can function as a test port. Alternatively, the fitment <NUM> can include any combination of large or small fittings. For example, fitment <NUM> could include one large fitting, two large fittings, one large fitting and one small fitting, three large fitting, and any other combination of the number and size of fittings as would be contemplated by those of skill in the art. Additionally, the fitment <NUM> can include fittings of different types. For example, fitment <NUM> can include one hose barb and one Luer fitting, two hose barbs and one Flaretek® fitting, or any other combination of fitting types.

In some embodiments, one or more fittings such as, for example, fitting(s) <NUM> or <NUM> can be integrally formed with the fitment <NUM> such that the fitment <NUM> and the fitting <NUM> or <NUM> form a single, unitary structure. <FIG> is an expanded cross-sectional view of a large hose barb <NUM> that has been integrally formed with the fitment <NUM>. As can be seen in <FIG>, the side walls <NUM>, <NUM> of the fitment are continuous with a neck <NUM>, tapered end region <NUM>, and inlet/outlet <NUM> of the fitting <NUM>.

In other cases, the fitting(s) <NUM> or <NUM> can be separate elements of fitment <NUM>. When provided separately from the fitment <NUM>, the fittings <NUM> or <NUM> can be inserted or otherwise connected to a port formed in the fitment <NUM>. In such an embodiment, the fitting(s) <NUM> or <NUM> can be formed of the same or different fluoropolymer as the fitment <NUM>.

Preferably, the fitting is formed from the same fluoropolymer as the fitment <NUM>. An example of a fitting that is provide as a component separate from a fitment is shown in <FIG> which depicts a hose barb fitting. As shown in <FIG>, hose barb fitting <NUM> includes a neck <NUM>, tapered end region <NUM>, and inlet/outlet <NUM>. Hose barb fitting <NUM> can be fit or welded to a section <NUM> of the fitment <NUM>.

In some embodiments, hose barb fittings <NUM>, <NUM> can be used to provide exit and entry ports to the bag assembly <NUM>. The inclusion of multiple barbs, such as the three-barb configuration shown in <FIG>, provides easy access for an end user of the bag, enabling multiple hose connections to either insert or withdraw media from the interior of the bag assembly. The inclusion of hose connections of multiple sizes, such as at least one large hose barb <NUM> and at least one small hose barb <NUM>, enables flexibility and compatibility with other components of a packaging, storage, or processing system. In some embodiments, a bag assembly, such as disclosed herein, can include a fitment having at least one <NUM> inch (<NUM>) hose barb and at least one <NUM> inch (<NUM>) hose barb.

Referring again to <FIG> and <FIG>, it can be seen that central opening <NUM> is enclosed by first and second inner sidewalls <NUM>, <NUM>. First inner sidewall <NUM> has an inner surface <NUM> and an outer surface <NUM> defining a first wall thickness. Similarly, second inner sidewall <NUM> has an inner surface <NUM> and an outer surface <NUM> defining a second wall thickness. Inner surfaces <NUM>, <NUM> face central opening <NUM>. The thickness of each sidewall <NUM>, <NUM> is substantially constant along the length of fitment <NUM>. In other words, the distance between inner surface <NUM> and outer surface <NUM> (or between inner surface <NUM> and outer surface <NUM>) is substantially constant along the length of fitment <NUM>. As a result, when fitment <NUM> cools after being heated during attachment of the walls <NUM>, <NUM> of the bag portion <NUM> to the fitment <NUM>, the fitment <NUM> is resistant to shrinking. The resistance of the fitment <NUM> to shrinking when cooled may facilitate formation of a more secure attachment between the fitment <NUM> and the walls <NUM>, <NUM> during bonding or welding.

Additionally, in some embodiments, attachments can be provided as part of the fitment <NUM> to hold and align a fitment during the assembly process, including during attachment of walls <NUM>, <NUM> to the sides walls <NUM>, <NUM> of the fitment. For example, fitment <NUM> can include projections <NUM>, shown in more detail in <FIG> and <FIG>. Projections <NUM> include holes <NUM> through which a hook or other fixture can be threaded to hold, align, or suspend the fitment <NUM> during welding operations.

<FIG> is a perspective view of a fitment 200B according to another embodiment of the disclosure. In particular, a fitment 200B is constructed in a substantially identical manner to fitment <NUM> except that the shape of an opening 210B is different than the shape of opening <NUM>. In addition, fitment 200B includes cavities <NUM>, <NUM>, which are defined, in part, by ribs <NUM>, <NUM>. The inclusion of cavities <NUM>, <NUM> reduces the amount of material present at the ends of fitment 200B relative to an otherwise identical fitment not including cavities <NUM>, <NUM>. Also, each of ribs <NUM>, <NUM> and walls <NUM>-<NUM> preferably has a constant thickness such that fitment <NUM> resists shrinking when cooled, which may in turn facilitate formation of a more secure attachment between the fitment <NUM> and the walls <NUM>, <NUM> during bonding or welding. This same result can also be accomplished by increasing the length of opening 210B. Such an arrangement is shown in <FIG> and <FIG>. Specifically, opening <NUM> is longer than opening 210B such that opening <NUM> takes up a larger percentage of the length of fitment <NUM>. Preferably, opening <NUM> extends along at least <NUM>% of the length of fitment <NUM>. <FIG> is a cross-sectional view of fitment 200B showing cavity <NUM> and rib <NUM>. Cavities <NUM>, <NUM> are formed using corresponding pins (not shown) during molding of fitment <NUM>.

A bag assembly, as described herein according to the various embodiments, can be formed without the use of adhesives, solvents or bonding. Eliminating the use of adhesives, solvents, or binders reduces the number of potential sources of leachables or extractables, which may enhance the overall purity of the final product. The bag assembly can be formed by attaching a first sheet of a fluoropolymer film to a second fluoropolymer film at their edges about each of their respective perimeters to form the first and second walls of the bag portion of the bag assembly. In other embodiments, the bag assembly can be formed from one or more sheet of fluoropolymer film that can be folded to provide the first and second walls that are then attached to one another to form the first and second walls of the bag assembly. In either case, the first and second walls can be attached to one another at their edges about a majority of their respective perimeters, leaving a portion at a top or a bottom of the bag portion unattached such that a fitment can be inserted between the first and second walls of the fluoropolymer film. Next, the first and second walls can be separated from one another at the unattached portion such that a fitment is able to be inserted between the two walls. Once the fitment is inserted and properly positioned between the two sheets walls, each of the first and second walls of the fluoropolymer film can be individually attached to the corresponding sidewall of the fitment. The first and second walls of the fluoropolymer film can be attached to one another by any suitable attachment known to those of skill in the art including, but not limited to heat bonding, impulse welding, platen welding, laser welding, ultrasonic welding or the like. The first and second walls of the film can be attached to the fitment using the same or a different attachment method. In one embodiment, a platen welding apparatus is used to attach the two walls to one another at their edges, and individually to each of the respective sidewalls of the fitment.

Once assembled, the bag assembly can undergo sterilization by gamma irradiation where the bag assembly can be subjected to at least <NUM> kGy and up to about <NUM> kGy, <NUM> kGy, <NUM> kGy, or <NUM> kGy of gamma radiation.

The disclosed bag assembly may be utilized in various applications where the storage of the chemical, biological or biopharmaceutical materials require a stable and sterile environment that is capable of meeting strict physical demands. In various embodiments, the bag assemblies may possess one or more of (i) the ability to withstanding sterilization by gamma irradiation, (ii) possess chemically stability in the presence of a wide range of materials, (iii) withstand cold temperatures including those as low as -<NUM>° C and more particularly, as low as <NUM> when subjected to cold crack testing as specified by ISO <NUM>:<NUM> (E), (iv) have a water vapor permeability of <NUM>/m<NUM>. bar, and (v) are UV stable.

In some embodiments, a bag assembly, as described herein, can be placed within an outer container, such as a rigid clam-shell overpack or an overpack bag, for handling or storage. In one embodiment, a storage system includes a bag assembly contained within an outer container. An exemplary storage system <NUM> is shown in <FIG>, with a bag assembly <NUM> contained within a rigid, clam-shell-type overpack <NUM>. Bag assembly <NUM> can alternatively be contained within a soft overpack bag (not shown). The clam-shell overpack <NUM> is shown in <FIG> with a lid <NUM> in an open position from a bottom portion <NUM> that contains the bag assembly <NUM>. Lid <NUM> and bottom portion <NUM> are connected by a hinge <NUM> located on one side of the overpack. A closure or locking mechanism <NUM> is attached to bottom portion <NUM> at hinge <NUM>. Locking mechanism <NUM> swivels at hinge <NUM> to fasten and release lid <NUM>. Overpack <NUM> is shown in <FIG> with lid <NUM> in a closed position and locking mechanism <NUM> fastened against lid <NUM>. Alternative structures and mechanisms for closing an overpack about a liner are contemplated, other than hinge <NUM> and locking mechanism <NUM>. For example, an overpack may be sealed shut. The overpack <NUM> can include one or more side ports <NUM> through which lines <NUM>, such as tubing connected to the fitting(s) or port(s) of the bag, can extend so that the bag can still be contained within the overpack during use.

Overpacks can be fabricated from metal, rigid plastic, or a combination of both metal and plastic. The overpack protects a bag contained therein and can be used during storage, transport, and also during use of the bag itself. In addition, the overpack limits expansion of the bags during the freezing process. In various embodiments, the bag is a bag assembly or a single-use liner. In some cases, the bag may be a bag assembly that does not require the use of an outer container or overpack, such that it can be considered to be a stand-alone, bag assembly. In other cases, the bag may be a single-use liner configured to fit within an outer bag or an overpack. Bag assemblies and liners are intended to be discarded following their initial use.

A <NUM> X <NUM> sample of an ethylenetetrafluoroethylene (ETFE) film having a single layer was subjected to cold crack testing per ISO <NUM>:<NUM>(E). The film sampled in this example can be used in the formation of the bag assembly, as described herein.

The sample was prepared for cold crack testing per ISO <NUM>:<NUM>(E), the steps of which included: cutting the <NUM> X <NUM> sample into <NUM> X <NUM> strips; obtaining ten test strips for each temperature to be evaluated; bowing the strips in the form of a loop and mounting six of the strips in the cold crack test fixture; and conditioning the strips for four hours at <NUM> +/-<NUM> per ISO <NUM>:<NUM> (E). Cold crack test fixtures, such as those used in this example, are commercially available from a variety of manufactures. Following conditioning of the six strips, the test fixture was placed in a freezer at -<NUM> until equilibrium was reached.

The test fixture was removed from the freezer, and the strips removed from the test fixture and visually inspected. The strips were determined to be broken or damaged if any one of the following imperfections were visually detected: trace of crack, points or dashes; trace of crack line; total rupture with no fragments; or total rupture with fragments.

If it was determined that none of the test strips were damaged or broken, the freezer temperature was then lowered by <NUM> and then the test was repeated with a set of new test strips. These steps were repeated until a temperature was reached at which <NUM>% of the test strips were determined to be broken or damaged by visual inspection.

Claim 1:
A bag assembly comprising:
a fitment having first and second sidewalls extending between opposing end points and defining a central opening, each of the first and second sidewalls having an inner surface and an outer surface defining a wall thickness therebetween, wherein the first and second side walls of the fitment have a constant thickness; and
a bag portion having first and second walls defining an interior, each of the first and second walls comprising at least one sheet of a fluoropolymer film, wherein a portion of each of the first and second walls of the bag portion are attached to each other along at least a portion of a perimeter of the bag portion up to the opposing end points of the fitment, and wherein a portion of each of the first and second walls of the bag portion are bonded individually to one of the first and second sidewalls of the fitment;
wherein the fitment comprises the same fluoropolymer as the first and second walls of the bag portion.