Patent Application
20170203868
The present invention relates to pouches or like articles for aseptic or sterile filling products therein, and more particularly, to pouches or like articles with fitments, and to methods of making such pouches, including methods of making such pouches with aseptic or sterile, and particle-free and/or pyrogen free interior surfaces.
Prior art pouches used to store aseptic or sterile products, such as pharmaceutical or food products, are typically manufactured in an environment where the interior surfaces of the pouches can be exposed to contamination during manufacturing. Accordingly, such pouches must be subjected to a sterilization process, either before or after filling the product therein, such as by terminal sterilization, or by sterilizing the pouch prior to aseptic or sterile filling the product therein. Terminal sterilization can be damaging to the product filled into the pouch and subject to the sterilization process. Gamma and other types of sterilization can be relatively costly, and if used to terminally sterilize, can damage the product filled into the pouch. If used to sterilize the pouch prior to aseptically or sterile filling the product into the pouch, such sterilization processes nevertheless can leave particulate matter, both viable and non-viable and associated pyrogens, in the interior chambers of the pouches, and thus in the products that are filled into the pouches. If such particulate matter is above a certain level, it can have an undesirable effect on the product. A viable particle is a particle that contains one or more living microorganisms. These can affect the sterility of a product, such as a pharmaceutical product, and generally range from about 0.2 μm to about 30 μm in size. A non-viable particle is a particle that does not contain a living microorganism but acts as transportation for viable particles. Pyrogens are fever-producing substances, which are metabolic products of microorganisms. Pyrogens are produced by many microorganisms including bacteria, yeasts and molds. Pyrogens can be damaging if injected into a human being. One of the drawbacks of prior art pouches and methods of manufacturing them is that they may not be free from particulate matter and associated pyrogens.
It is an object of the present invention to overcome one or more of the above-described drawbacks and/or disadvantages of the prior art.
In accordance with a first aspect, the present invention is directed to a method comprising the following steps:
In some embodiments of the present invention, step (i) includes blown film extrusion molding (BFM) the tubular film. In some embodiments, step (i) includes molding a multiple layer tubular film including an inner layer defining a first melting temperature and an outer layer defining a second melting temperature. The first melting temperature of the inner layer is higher than the second melting temperature of the outer layer. In some such embodiments where the tubular film includes multiple layers, step (i) includes co-extrusion blown film molding (CEBFM) the tubular film. In some embodiments, the BFM or CEBFM includes blowing or otherwise introducing a flow of micro-filtered air and/or other gas through the interior of an extrusion or co-extrusion head and the tubular film. Preferably, an inner surface of the tubular film is at bactericidal temperature during step (i).
In some embodiments of the present invention, step (iv) includes molding a flange or base of the fitment in a first molding station, and over-molding a septum to the flange or base in a second molding station. In some such embodiments, the mold is a rotary mold, and step (iv) includes rotating the mold from the first molding station to the second molding station. Some embodiments further comprise rotating the mold containing the base or flange of the fitment, and presenting the base or flange of the fitment to a secondary molding station for over-molding the septum of the fitment thereto. Some embodiments comprise over-molding a base of the fitment onto the empty pouch, and then over-molding the septum to the base to thereby form a sealed, empty pouch. Other embodiments comprise over-molding the base and septum of the fitment to the pouch in the same mold. Some such embodiments comprise over-molding the base and septum of the fitment to the pouch at the same time. In some such embodiments, the base and septum of the fitment are made of the same or substantially the same material, such as a thermoplastic elastomer. Some embodiments further comprise opening the mold, and upon opening the mold, actuating a cam or other actuator to move a septum portion of the fitment into an at least partially closed position. Some embodiments of the present invention further comprise introducing an over-pressure of micro-filtered air and/or other gas through an open area of the mold for over-molding the fitment and/or septum of the fitment, and preventing the collection of particles on at least the interior surfaces of the molded fitment.
Some embodiments of the present invention comprise over-molding the septum onto a hinged portion of the fitment and forming a one-piece or integral fitment and septum. Some embodiments further comprise moving the hinged septum of the fitment into an at least partially closed position and preventing exposure of the inner surfaces of the septum and fitment to the ambient environment. Some such embodiments further comprise over-molding the septum to a hinged portion of the fitment, moving the septum about the hinge to close the fitment, and forming a sealed, empty pouch. In some such embodiments, step (iv) includes over-molding the fitment to the outer surface of the pouch in a rotary mold, rotating the mold and then over-molding the septum to the hinged portion of the fitment, automatically moving the septum about the hinge and closing the fitment, and de-molding the sealed, empty pouch from the mold.
Some embodiments of the present invention further comprise over-molding the fitment in a first mold cavity, molding a septum of the fitment in a second mold cavity, moving at least one of the first or second mold cavities toward the other, assembling the septum and fitment, and forming a sealed, empty pouch. In some such embodiments, the fitment is over-molded in a first mold, such as a cubic or rotary mold, and the septum is molded in a second mold, such as a cubic or rotary mold. Some such embodiments further comprise rotating the first and/or second molds of, for example, a double cubic mold, to align the septum and fitment, moving the aligned septum and/or fitment toward the other to assemble the septum and fitment, and de-molding the sealed, empty pouch. Some embodiments further comprise blowing or otherwise directing an over-pressure of micro-filtered air and/or other gas into or through an open area of the molds.
In some embodiments of the present invention, step (iii) includes sealing the flattened tubular film at spaced locations, and then cutting the sealed film at the spaced locations, to thereby form a plurality of empty pouches. Some embodiments comprise forming an aperture through the tubular film, and over-molding the fitment to the pouch along the periphery of or otherwise about the pouch aperture. Some embodiments comprise forming the pouch aperture by cutting the aperture through the one or more layers of the tubular film. Other embodiments comprise forming the pouch aperture by sealing an edge portion of the pouch at spaced locations relative to each other, and thereby forming the pouch aperture between sealed edge portions. In some embodiments, the pouch aperture is formed just prior to inserting the pouch into the mold. Some embodiments further comprise forming the pouch aperture and over-molding the fitment onto the periphery of or otherwise about the pouch aperture to seal the aperture. Some embodiments further comprise blowing or otherwise directing micro-filtered air and/or other gas into or through an opening of the mold for over-molding the fitment to the pouch.
In some embodiments of the present invention, step (iii) includes thermally sealing and/or cutting the tubular film. In some such embodiments, the cutting occurs substantially simultaneously with, or immediately upon, sealing. In some embodiments, the thermal sealing is performed with one or more of an impulse heat sealer, a continuous heat sealer, a hot bar heat sealer, a hot wire sealer, an induction sealer, and an ultrasonic welder or sealer.
In some embodiments of the present invention, the fitment and the outer surface of the film include the same or substantially the same polymer. In some such embodiments, both the outer surface of the film and at least the portion of the fitment over-molded thereto are polypropylene. In some embodiments, an inner layer of the tubular film is a copolyester elastomer (COPE).
Some embodiments of the present invention further comprise cutting or otherwise forming an aperture through a sealed edge portion of a pouch, and over-molding a fitment onto opposing sides of the pouch and about the periphery of the pouch aperture to seal the aperture. In some such embodiments, the pouch aperture is formed prior to insertion of the pouch into the mold for over-molding the fitment thereto, or is formed within the mold prior to over-molding the fitment thereto. In some embodiments, the pouch aperture is formed in the pouch with the pouch located adjacent to, or otherwise in close proximity to, and/or is formed immediately prior to insertion of the pouch into, the mold for over-molding the fitment thereto. Some embodiments further comprise maintaining the pouch in a flattened condition during forming the pouch aperture therethrough, and/or directing an over-pressure of micro-filtered air or other gas onto the pouch during formation of the pouch aperture therein.
Some embodiments of the present invention further include over-molding a flexible portion of the fitment by forming a reduced cross-sectional thickness as compared to other portions of the fitment and/or by forming the fitment or a portion thereof from a flexible material, such as the same or substantially the same material used to form the septum. Some such embodiments further include molding a fitment including a base that is over-molded to the outer surface of the pouch and extends along or about the periphery of the pouch aperture. A port of the fitment extends from the base and defines a fitment aperture in fluid communication with the pouch aperture. In some embodiments, a junction of the base and port defines a reduced cross-sectional thickness to allow flexing of the base and/or port relative to the other. Some embodiments further include over-molding a septum onto a septum support, and moving the over-molded septum into a port aperture to at least partially close the port aperture and prevent exposure of the interior surfaces of the septum and port aperture to the ambient environment. Some embodiments further comprise molding the fitment with a hinge and septum support connected by the hinge to the fitment, over-molding the septum to the septum support, and moving the over-molded septum about the hinge at least partially into the port aperture.
In some embodiments of the present invention, during step (iv), the over-molding of the fitment at least partially melts an outer layer of a multiple layer tubular film and thermally bonds the fitment thereto, but does not melt an inner layer of the tubular film, and thereby maintains a separateness between the opposing inner surfaces of the inner layer at the over-molded fitment.
In accordance with another aspect, the present invention is directed to a sealed, empty pouch, wherein the interior of the pouch is particle free. The pouch is made in accordance with the following method:
In some embodiments of the present invention, step (i) includes molding a multiple layer tubular film including an inner layer defining a first melting temperature and an outer layer defining a second melting temperature. The first melting temperature of the inner layer is higher than the second melting temperature of the outer layer. In some embodiments, the inner surfaces of the pouch are sterile and sealed with respect to ambient atmosphere.
In accordance with another aspect, the present invention is directed to a pouch comprising a tubular film including an inner surface and an outer surface, a first end edge portion extending from approximately one side of the pouch to another side of the pouch, and a second end edge portion located on an opposite end of the pouch relative to the first end edge portion, and extending from approximately one side of the pouch to another side of the pouch. The opposing surfaces of the tubular film are sealed to each other at the first end and second end edge portions, and define an interior chamber between opposing inner surfaces of the tubular film. In some embodiments, the interior chamber extends from the first end to the second end, and from one side to another side of the pouch. The pouch defines a pouch aperture in fluid communication with the interior chamber, and extending through the tubular film and/or between opposing edge portions of the pouch. A fitment is over-molded to the outer surface of the pouch along a periphery of the pouch aperture. The outer surface of the tubular film is at least partially melted and thermally bonded to the fitment to thereby form a fluid-tight seal between the pouch and fitment about the pouch aperture.
In some embodiments of the present invention, the pouch comprises a multiple layer tubular film including an inner layer and an outer layer. The inner layer defines a first melting temperature and the outer layer defines a second melting temperature. The first melting temperature of the inner layer is higher than the second melting temperature of the outer layer. The outer layer of the tubular film is at least partially melted and thermally bonded to the fitment, but the inner layer of the tubular film is not melted and separateness is maintained between the opposing inner surfaces of the inner layer at the over-molded fitment.
In some embodiments of the present invention, the interior chamber of the pouch is hermetically sealed with respect to the ambient atmosphere. In some such embodiments, the interior chamber of the pouch is aseptic and/or sterile. In some embodiments, the interior chamber of the pouch is particle free. In some embodiments, the interior chamber of the pouch is pyrogen free. In some embodiments, the interior chamber of the pouch is empty.
In some embodiments of the present invention, the over-molded fitment includes a flexible portion defined by (i) a reduced cross-sectional thickness as compared to other portions of the fitment and/or (ii) a flexible material, such as the same or substantially the same material used to form the septum of the fitment. In some such embodiments, the fitment includes a base over-molded to the outer layer of the pouch and extending along or about the periphery of the pouch aperture. A port of the fitment extends from the base and defines a fitment aperture in fluid communication with the pouch aperture. In some such embodiments, a junction of the base and port defines a reduced cross-sectional thickness and/or is formed of a flexible material that allows flexing of the base and/or port relative to the other. In some embodiments, the fitment includes a septum support and an elastic septum over-molded to the septum support. In some such embodiments, the septum support is fixedly secured to the port and the septum seals the port aperture. In some embodiments, the septum is elastic and forms axial and/or radial seals between the septum and port. In some embodiments, the septum support is movable between a first position for over-molding the septum thereto, and a second position for moving the over-molded septum into the port aperture to at least partially close the port aperture and prevent exposure of the interior surfaces of the septum and port aperture to the ambient environment. In some such embodiments, the fitment includes a hinge that movably connects the septum support to the fitment.
In some embodiments, the fitment includes a septum over-molded thereto and hermetically sealing the fitment and pouch aperture with respect to ambient atmosphere. The fitment is penetrable by a needle or other injection member for penetrating the septum, and sterile or aseptic filling a substance thereto into the interior chamber. The resulting penetration aperture in the septum is resealable by applying one or more of heat, radiation, liquid sealant, or mechanical closure thereto.
In some embodiments of the present invention, a pouch aperture extends through outer and inner layers of a multiple layer tubular film on opposing sides of the tubular film relative to each other. The fitment base is over-molded to the outer layer of the tubular film on opposite sides of the tubular film relative to each other. In some embodiments, the pouch aperture extends through an end edge portion of the pouch, and the fitment base extends over the respective end edge portion and over opposite sides of the pouch relative to each other.
In some embodiments of the present invention, the pouch further includes a closure overlying the septum and forming a fluid-tight seal between the septum and the ambient atmosphere. In some such embodiments, the closure is substantially inflexible. In some embodiments, the closure if formed of a hot-melt adhesive sealant overlying the septum and bonded to a septum support extending about a periphery of the septum. In some such embodiments, the hot-melt closure substantially conforms to the shape or morphology of the septum at the interface therebetween, but is not bonded thereto.
In some embodiments of the present invention, the pouch defines a first interior chamber and a second interior chamber, and a sealed portion extending between the first and second chambers. In some such embodiments, the sealed portion defines a frangible seal. In some embodiments, the frangible sealed is defined by opposing surfaces of the tubular film sealed to each other. Some embodiments further comprise a first pouch aperture in fluid communication with the first interior chamber, a second pouch aperture in fluid communication with the second interior chamber, a first fitment over-molded to the outer surface along a periphery of the first pouch aperture, and a second fitment over-molded to the outer surface along a periphery of the second pouch aperture. Some such embodiments further comprise a third pouch aperture in fluid communication with the second interior chamber, and a third fitment over-molded to the outer surface along a periphery of the third pouch aperture. In some embodiments, the second and third fitments are located on substantially opposite sides of the pouch relative to each other.
In accordance with another aspect, the present invention is directed to a pouch comprising a tubular film including an inner surface and an outer surface, a first end edge portion extending from approximately one side of the pouch to another side of the pouch, and a second end edge portion located on an opposite end of the pouch relative to the first end edge portion and extending from approximately one side of the pouch to another side of the pouch. The opposing surfaces of the tubular film are sealed to each other at the first end and second end edge portions, and define an interior chamber between opposing inner surfaces of the tubular film extending from the first end to the second end, and from one side to another side of the pouch. The pouch defines a pouch aperture that is in fluid communication with the interior chamber and extends through the outer and inner surfaces of the tubular film on at least one side of the pouch and/or between opposing edge portions of the pouch. The pouch further includes first means over-molded to the outer surface of the pouch along a periphery of the pouch aperture, for sealing the pouch aperture and introducing a substance therethrough for filling the interior pouch chamber with the substance and/or withdrawing a substance in the pouch chamber therethrough. The outer surface of the tubular film is at least partially melted and thermally bonded to the first means to thereby form a fluid-tight seal between the first means and pouch about the pouch aperture.
Some embodiments of the present invention further comprise second means over-molded to the first means for sealing the first means and for filling the interior pouch chamber therethrough. In some embodiments, the first means is a fitment and the second means is an elastic septum.
In accordance with another aspect, the present invention is directed to a method comprising the following steps: (i) penetrating an elastic septum of a device with a needle or other injection member; (ii) introducing a substance through the needle and into a sealed chamber in fluid communication with the elastic septum; (iii) withdrawing the needle from the septum; (iv) sealing a resulting needle hole in the septum by introducing a liquid hot-melt adhesive sealant onto the septum and covering the septum and the resulting needle hole with the liquid hot-melt sealant; and (v) allowing the liquid hot-melt sealant to cool, transition from a liquid to a solid, and form a substantially inflexible closure overlying the septum. In some embodiments of the invention, the device is a pouch, a vial, a syringe, or a container.
In some embodiments of the invention, the method further comprises heating the liquid hot-melt sealant to a bactericidal temperature, applying the liquid hot-melt sealant onto the septum at the bactericidal temperature, and sterilizing the interface between the hot-melt sealant closure and the septum. Some embodiments further comprise fixedly bonding the liquid hot-melt sealant to a septum support extending about a periphery of the septum, and forming a fluid-tight seal between the septum and ambient atmosphere. Some embodiments further comprise substantially conforming the hot-melt sealant to the shape or morphology of the septum at the interface of the sealant and septum, but not bonding the sealant to the septum.
One advantage of the present invention, and/or of the disclosed embodiments thereof, is that the inner surface of the pouch may be free of particulate matter and pyrogens. Another advantage is that the inner surface of the pouch may be sterile without requiring the pouch to be subjected to additional sterilization processes, such as gamma or other forms of radiation, or terminal sterilization. Yet another advantage is that the methods of the invention may prevent exposure of the inner surface of the pouch to the ambient environment from the time of formation until final assembly of the pouch, thus allowing for the formation of a pouch with a sterile, particle-free and pyrogen-free interior chamber. The interior chamber may be sterile or aseptically filled through the elastic septum with a closed needle or like injection member such that the sterile or aseptic product may be maintained sterile, particle-free and/or pyrogen free within the sealed interior chamber of the pouch.
Another advantage of embodiments of the invention is that the septum and fitment can be closed within the mold, such as by rotation and/or other movement of rotary molds, or by a robot, such as a pick and place robot, that picks the pouch over-molded with the fitment, and places the septum into the fitment to seal the fitment and pouch, right off or adjacent to the mold. As a result, the inner surfaces of the fitment, its septum, and the pouch, are prevented from exposure to the ambient environment.
Yet another advantage is that the pouch may define multiple compartments or interior chambers separated by frangible portions, such as frangible seals, allowing the pouch to be filled with different products and/or products in different chambers, that may be premixed prior to dispensing or delivery by breaking the frangible seal(s), and/or the products may be delivered/dispensed in series from one chamber, and then another, such as to first dispense a saline that may be used, for example, to purge an IV line, and to then dispense the API for delivery through the line to the patient.
Other objects and/or advantages of the present invention, and/or of the embodiments thereof, will become more readily apparent in view of the following detailed description and accompanying drawings.
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After the pouch 16 is inserted into the first mold 30, the first mold is rotated about 90° to a first molding station 40, and the fitment 28 is over-molded to the pouch in the first molding station. The base 42 of the fitment is over-molded to the outer surface/layer 14 of the pouch along the periphery of the pouch aperture 38 to thereby seal the pouch aperture with respect to the ambient atmosphere along its periphery. The over-molding of the fitment 28 at least partially melts the outer surface/layer 14 of the tubular film, and thermally bonds the fitment base 42 thereto, but does not melt the inner surface/layer 12 of the tubular film. As a result, separation is maintained between the opposing inner surfaces of the inner layer 12 at the over-molded fitment, and thus the integrity of the sealed, empty, sterile, particle-free interior chamber 26 of the pouch is not disturbed. In some such embodiments, the inner surface/layer 12 has a higher melting temperature than the outer surface/layer 14, helping to prevent melting of the inner surface/layer 12. As shown in
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After inserting the pouch into the mold 130, the mold is rotated about 90° to present the pouch to the first molding station 140 where the fitment 128 and integral septum support/mold ring 134 are over-molded thereto with the base 142 sealed along the periphery of the pouch aperture 38. The base 142 of the fitment is over-molded to the outer layer 14 of the pouch along the periphery of the pouch aperture 38 to thereby seal the pouch aperture with respect to the ambient atmosphere along its periphery. The over-molding of the fitment 128 at least partially melts the outer layer 14 of the tubular film and thermally bonds the fitment base 142 thereto, but does not melt the inner layer 12 of the tubular film, and thereby maintains separateness between the opposing inner surfaces of the inner layer 12 at the over-molded fitment and does not disturb the integrity of the sealed, empty, sterile, particle-free interior chamber 26 of the pouch.
The mold 130 is then rotated another about 90° to present the fitment 128 and integral molded ring 134 thereof to a second molding station 146 where the septum 132 is over-molded to the integral mold ring 134. Then, as indicated by the arrow in
The sealed, empty pouch may be sterile or aseptically filled through the elastic septum 132 with a closed needle or like closed injection member. The fitment is penetrable by a needle or other injection member (not shown) for penetrating the septum and sterile or aseptically filling a substance into the interior chamber 26 of the pouch. The resulting penetration aperture in the septum is resealable by applying one or more of heat, radiation, liquid sealant, or mechanical closure thereto. The closed needle filling apparatus and process, and the septum, may take the form of any of the apparatus and methods disclosed in the following patents and patent applications, which are hereby incorporated by reference in their entireties as part of the present disclosure: U.S. patent application Ser. No. 14/214,890, filed Mar. 15, 2014, entitled “Controlled Non-Classified Filling Device and Method,” which claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/798,210, filed Mar. 15, 2013; U.S. patent application Ser. No. 15/267,131, filed Sep. 15, 2016, entitled “Septum That Decontaminates by Interaction With Penetrating Element,” which claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 62/219,035, Sep. 15, 2015; U.S. Design patent application Ser. No. 29/539,571, filed Sep. 15, 2015, entitled “Septum;” U.S. patent application Ser. No. 14/636,954, filed Mar. 3, 2015, entitled “Modular Filling Apparatus and Method,” which is a divisional of similarly titled U.S. patent application Ser. No. 13/861,502, filed Apr. 12, 2013, now U.S. Pat. No. 8,966,866, which, in turn, claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/686,867, filed Apr. 13, 2012; U.S. patent application Ser. No. 13/450,306, filed Apr. 18, 2012, entitled “Needle With Closure and Method,” which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/476,523, filed Apr. 18, 2011, entitled “Filling Needle and Method;” U.S. patent application Ser. No. 13/864,919, filed Apr. 17, 2013, entitled “Self Closing Connector,” which claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/784,764, filed Mar. 14, 2013, and similarly titled U.S. Provisional Patent Application Ser. No. 61/635,258, filed Apr. 18, 2012, and similarly titled U.S. Provisional Patent Application Ser. No. 61/625,663, filed Apr. 17, 2012; U.S. patent application Ser. No. 13/917,562, filed Jun. 13, 2013, entitled “Device With Penetrable Septum, Filling Needle and Penetrable Closure, and Related Method,” which claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/799,744, filed Mar. 15, 2013, and similarly titled U.S. Provisional Patent Application Ser. No. 61/659,382, filed Jun. 13, 2012; U.S. patent application Ser. No. 14/708,196, filed May 9, 2015, entitled “Self Closing and Opening Filling Needle, Needle Holder, Filler and Method,” which claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/991,561, filed May 11, 2014, and similarly titled U.S. Provisional Patent Application Ser. No. 61/991,467, filed May 10, 2014; U.S. Provisional Patent Application Ser. No. 61/991,557, filed May 11, 2014, entitled “Self Closing and Opening Filling Needle, Needle Holder, Filler and Method;” U.S. Provisional Patent Application Ser. No. 61/991,474, filed May 10, 2014, entitled “Self Closing and Opening Filling Needle, Needle Holder, Filler and Method;” and U.S. patent application Ser. No. 15/238,011, filed Aug. 16, 2016, entitled “Device With Sliding Stopper and Related Method,” which is a divisional of similarly titled U.S. patent application Ser. No. 14/208,030, filed Mar. 13, 2014, now U.S. Pat. No. 9,415,885, which, in turn, claims the benefit of similarly titled U.S. Provisional Patent Application Ser. No. 61/799,423, filed Mar. 15, 2013.
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In addition, or alternatively, the fitment 228 contains a color indicator that signifies the sterility of the septum 232 and/or the pouch 216 (or its interior chamber 226). The color indicator changes color upon heat or radiation exposure, e.g., gamma radiation exposure. Upon exposure to sufficient heat or radiation, the color indicator changes to a color signifying that the septum 232 and/or the pouch 216 is sterile. In some embodiments, the color indicator is blended into the material forming the septum 232. In yet other embodiments, the colored sterility indicator is located elsewhere on pouch 216 or its fitment 228.
As may be recognized by those of ordinary skill in the pertinent art based on the teachings herein, the labels may include any of numerous different features that are currently known, or that later become known, including different features for identifying the pouch, such as a bar code, computer chip, or other optical or electronic means for identifying, monitoring and/or tracking the pouch. Alternatively, the label may include only an identifier, such as an RFID tag, or a dosimeter, but not both. In addition, the label-receiving marginal edge portion 264 need not include a label at all, but rather may receive an RFID tag, dosimeter and/or other device therein without a label, or may receive one or more such devices separate from a label. Accordingly, the label-receiving marginal edge portion may serve any of numerous different purposes, and/or may receive any of numerous different devices, that are currently known, or that later become known. Still further, the label-receiving marginal edge portion may be located on any marginal edge portion of the pouch, and need not extend along the entire respective edge portion. Such an embodiment is shown in
The illustrated pouch 216 was needle filled through the left-hand port 252, and the penetrated septum 232 was re-sealed with a liquid sealant 243. In the illustrated embodiment, the liquid sealant 235 is a hot-melt adhesive sealant. As shown in
Another advantage of the hot-melt adhesive sealant 243 is that it allows for improved quality control. Upon or within a set time following application of the hot-melt sealant to the septum 232, a temperature sensor (not shown) senses the temperature of the hot-melt sealant and transmits same to a controller (not shown). The controller compares the sensed temperature to an acceptable range, or otherwise determines whether the applied sealant temperature is sufficiently high to have a bactericidal effect on the surfaces of the septum. In addition, the temperature sensor may measure the temperature profile across the surface of the septum, to assess whether the hot melt sealant fully covers the septum. For example, if a portion of the scanned temperature profile is below a lower temperature threshold, this may indicate a bare or thin spot in the overlying sealant, and thus the controller can flag the respective product for rejection or further inspection. Alternatively, a computer vision camera may be used to visually monitor the application of the hot-melt sealant, and flag any seals that do not meet or substantially conform to a required visual seal profile.
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As can be seen, the base 342 of the fitment is thermally bonded to the tab 370 of the pouch and forms a fluid-tight seal therebetween, and the septa 332 are formed within the respective septum supports 334 and thermally bonded thereto. Because of its formation about the core pin 339, the elastic fitment 328 defines an elongated aperture 380 in the right side thereof in
One advantage of the pouch 316 is that the core pin (or the tab-penetrating portion thereof) is inserted into the pouch aperture during molding, and thus is interposed between the opposing sides of the tubular film, during over-molding the fitment thereto. As a result, the core pin provides a thermal barrier between the opposing sides of the film that thermally insulates one side from the other and otherwise prevents the opposing sides of the film from bonding to each other during over-molding. Accordingly, this configuration obviates the need to use a multiple layer tubular film where the inner layer of the film defines a higher melting temperature than the outer layer of the film, as described above. In addition, during over-molding the cure pin is heated to a bactericidal temperature, thus killing any bugs, germs or other contaminants that might come into contact with it during over-molding and providing an over-molded fitment with a sterile interior. Another advantage of the pouch 316 is that the fitment 328, and in particular the base 342 thereof, is formed of a flexible or elastic material, which allows the fitment to flex outwardly and provide an unobstructed passageway for filling the pouch therethrough. In some embodiments of the invention, a closed needle is used to penetrate a septum of the fitment, and the closed needle is not opened until it passes through the septum and is in fluid communication with the interior of the pouch. Then, the flow of fluid from the closed needle into the pouch can operate to delaminate the opposing sides of the pouch film as the fluid is introduced therein. Another advantage of the pouch 316 is that the fitment 328 can be made of a thermoplastic elastomer having a relatively low melting temperature which, in turn, allows the resulting slot in the fitment after withdrawal of the core pin therefrom to be easily sealed, such as by applying a thermal pinch seal right off the mold upon de-molding the pouch. Another advantage is that, if desired, the pouch can be made of essentially two materials, a thermoplastic elastomer for the fitment, including the septa, and polypropylene(s) for the septum supports and pouch. Such materials are recyclable, and thus facilitate recycling the pouches after disposal.
The rigid rings or septum supports 334, 334 effectively rigidify the otherwise flexible fitment and provide rigid surfaces adjacent to each septum to allow gripping by a user, such as a nurse or other practitioner, for purposes of, for example, inserting a syringe needle through the septum, and/or for mounting or otherwise engaging the fitment in a sterile or aseptic filling machine. The septum supports 334, 334 can be molded and then inserted into the fitment mold for over-molding the fitment to the septum supports and to the pouch, or the septum supports can be molded in a first molding station of mold, and the fitment can be over-molded to the septum supports and pouch in a second molding station, such as in the first and second stations of a rotary mold, such as a rotary cubic mold, as described above. In another embodiment, the septum supports are molded in a first molding station, the septa are over-molded to the septum supports in a second molding station, and the fitment is over-molded to the septum supports and pouch in a third molding station, such as in the molding stations of a rotary mold, such as a rotary cubic mold, as described above. If desired, the over-molded fitment can be formed of a different material than the septa, and can be over-molded to the septa and/or to the septum supports. One advantage of molding the septum supports in the same mold as used for over-molding the fitment is that it eliminates the need to move the septum supports from one mold to another and otherwise eliminates the need to handle the septum supports prior to over-molding the fitment. However, if desired, the septum supports can be molded in a first mold, and moved, such as automatically by a pick and place robot or like device, from a first mold to a second mold where the fitment is over-molded to the septum supports and pouch. In some such embodiments, the mold may define multiple cavities in a single or respective injection press, where each fitment is over-molded to a pouch and septum support in a respective cavity, and the cavities are interconnected by runners. In each case, the over-molding of the fitment ensures that the interior surfaces of the fitment and the interfaces of the fitment and pouch are heated to a sufficiently high temperature by virtue of the heated core pin(s), mold and molten plastic injected into the mold, to maintain the sterility of the sealed, empty pouch, including its fitment.
Another advantage of the pouch 316 is that the septa are oriented at approximately 90° relative to each other. As can be seen, one septum 332 is approximately aligned with the elongated axis of the pouch and thus is substantially vertically oriented when the pouch is hung from its grommet 360. The other septum 332 is aligned with an axis approximately perpendicular to the elongated axis of the pouch and thus is substantially horizontally oriented when the pouch is hung from its grommet 360. If desired, one septum may be used for filling and the other septum for dispensing or otherwise withdrawing a fluid or other substance from the sealed chamber 326. In one embodiment, the horizontally oriented septum is used for filling and the vertically oriented septum is used for dispensing/withdrawing (although such roles/functions may be reversed). One advantage of such configuration is that a syringe needle or sterile connector, such as for sampling, may be inserted through the vertically oriented septum. This, in turn, allows the needle/connector tip to be located within the port aperture within the respective port 352 to thereby minimize any ullage or residue within the pouch upon emptying the pouch.
In
As shown in
As shown typically in
In
As shown in
When the pouch 516 is filled in this manner, the filling may be performed a non-sterile fashion, if desired. The entire sealed pouch, including the filled substance, may then be sterilized, such as by gamma radiation or heat (autoclaved) where the substance 576 will tolerate the selected sterilization procedure. In some embodiments, the pouch 516 may include one or more sterility indicators, as described herein, that change color during the sterilization procedure to indicate that the sealed pouch 516 and substance 576 are sterilized. Once the pouch 516 is sterilized, the substance 576 is maintained sterile within in the sealed pouch 516 with no exposure to the environment. In some embodiments, the filling may take place under a flow of micro-filtered and/or sterile air and/or other gas as described herein to prevent the collection of undesired particles within the pouch 516.
Once the pouch 516 and substance 576 are sealed within the pouch and sterilized, the ports 552 may be utilized as elsewhere described herein to remove substance from the pouch 516 and/or add substance to the pouch 516 in a sterile manner. For example, one or more of the septa 332 may be pierced by a needle or injection member, substance added or withdrawn as desired, and the pierced septum resealed as elsewhere described herein.
In some embodiments where the substance 576 is a powder, the pouch 516 may be sterile filled with sterile fluid, solvent or diluent through a septum 532. The powder 576 may then be dissolved into or otherwise combined with fluid by added fluid. To assist in this process, and to promote even distribution of formulation within the pouch 516, the pouch 516 may be squeezed, manipulated, vibrated, or shaken. The resultant fluid may then be withdrawn through one of the septa 532 as described herein. Similarly, in embodiments where a high viscosity fluid is filled into the pouch, a diluent may be sterile filled into the pouch 516 through a septum 532 to sufficiently reduce the viscosity of the fluid so that it can be removed from the pouch through a septum 532.
In
In the illustrated embodiment, the frangible seal 680 extends from side 620 to side 622. It should be understood by those of ordinary skill in the art that though in the illustrated embodiment the frangible seal 680 extends from side 620 to side 622, the frangible seal may extend between any of the first end marginal edge portion 618, the second end marginal edge portion 620, and the sides 620, 622 as desired. Further, while the illustrated frangible seal 680 is linear, the frangible seal may have any desired configuration that separates the interior 626 into multiple chambers, e.g., curvilinear, curved, or having multiple contiguous linear, curved and/or curvilinear segments. In addition, though the illustrated frangible seal 680 extends perpendicularly to the sides 620, 622, the frangible seal 680 may extend at any desired angle. Moreover, though the illustrated frangible seal 680 is located on the pouch 616 where the chambers 626a, 626b are of approximately the same size, the frangible seal 680 may be located so as to create chambers of different sizes, as illustrated in
In the illustrated embodiment, the pouch 616 has three fitments 628. One fitment is located in fluid communication with chamber 626a, and two fitments are located in fluid communication with chamber 626b. Other embodiments may contain more or fewer fitments. In addition, though the two fitments in fluid communication with chamber 626b are located at side 620 and side 622 respectively, the fitments may be located on the same side as each other (see, as an example,
The frangible portion 680 is breakable in response to pressure in one or both of the chambers 626a, 626b exceeding a substantially predetermined threshold pressure that will break the frangible portion 680. In one such embodiment, the frangible portion 680 is breakable by engaging and squeezing the pouch 616 at a location of one of the chambers so as to increase the pressure of substance in that chamber to or beyond the threshold pressure. A threshold pressure should be provided so as to be lower than the pressure that would separate the layers of the pouch 616 at the first and second end marginal edge portions 618, 620 or cause the material of pouch 616 to tear, rupture or burst. In embodiments where the frangible portion 680 may be broken by manually engaging and squeezing the pouch, the threshold pressure preferably is achievable without undue effort by the user. On the other hand, the threshold pressure may be provided so as to be sufficiently high to prevent unintended breaking of the frangible portion.
The frangible portion 680 may be formed in any of numerous different ways, that are currently known, or that later become known. In one embodiment, the frangible portion 680 may be formed by sealing the opposing inner surfaces or layers of the pouch 616 together in a similar manner or process as to how the inner surfaces or layers may be sealed to form the end marginal edge portions 618, 624 of the pouch, e.g., by heat sealing the inner surfaces or layers of the pouch together at the location of the frangible portion 680. Providing a desired threshold breaking pressure of the frangible portion, e.g., less than the threshold breaking pressure of the end marginal edge portions 618, 620 and the pouch material, may be accomplished in any suitable manner. One such way is to perform the heat sealing of the frangible portion 680 at a lower temperature, lower pressure and/or shorter time than the sealing of the end marginal edge portions 618, 620, so as to provide a seal that is not as strong as at the end marginal edge portions 618, 620, but strong enough to maintain the seal between the chambers 626a, 626b until it is desired to be broken. Another way, which may be used alternatively to or in addition to the process described in the preceding sentence, is to form the frangible seal 680 with a width (e.g., the transverse distance the seal extends between the chamber 626a, 626b) that is less than the width of the seals at the end marginal edge portions 618, 620. Accordingly, the area of the frangible seal would be less than the area of the seal(s) at the end marginal edge portions 618, 624, and thus at a reduced strength (threshold pressure) compared thereto. As illustrated in
The pouch 626 may be used, for example, to fill each chamber 626a, 626b with a different substance.
Next, as seen in
Those of ordinary skill in the art should understand that, while in the illustrated embodiment the fitment 628 located at the side 620 of the pouch 616 is used to fill the chamber 626b, and the fitment 628 located at the side 622 of the pouch 616 is used to empty the chamber 626b, the fitment 628 located at the side 622 may be used for filling and the fitment 628 located at the side 620 may be used for removal. It should also be understood that in other embodiments chamber 626a has multiple fitments, such that substance may be first removed from chamber 626a and the frangible seal 680 may be broken by pressurizing the substance in the chamber 626b.
The above-described process may be used, for example, to sequentially dispense substances 676b and 676a from the pouch 616. Though any desired substances may be filled into the pouch 616 and sequentially dispensed, in one embodiment, substance 676b may be saline and substance 676a may be a drug, e.g., Carboplatin. The saline 676b may be dispensed from the pouch 616 to purge or clean the flow line 684. The drug 676a may then be dispensed without contacting or interacting with other substances (other than saline) in the fluid line 684.
In other embodiments, the pouch 616 may be used to mix different substances. It may be desirable to mix or otherwise combine substances only shortly before dispensing, e.g., where the mixture is not sufficiently stable or degrades if mixed too far in advance of dispensing, as available with conventional formulation manufacturing. Mixing at or close to the time of dispensing may provide enhanced tolerance, absorption, transport and/or bioavailability of the mixture.
To mix the substances 676a, 676b prior to dispensing, the sequence illustrated by
In yet further embodiments, the pouch 616 may be used to dispense multiple portions of the same substance at different times. In such embodiments, the chambers 626a, 626b are filled with the same substance in the manner describe above with respect to
In
In some embodiments, the fitments(s) are not over-molded to a pouch. Rather, the fitment is formed separately from the pouch, such as by molding in the above described molds or separate molds, and then thermally sealed to the pouch in a manner that forms a single, continuous sealed interface between the fitment and the pouch. The sealed interface keeps the inner surfaces of the pouch sealed from ambient atmosphere. The heat sealing may be performed with one or more of an impulse heat sealer, a continuous heat sealer, a hot bar heat sealer, a hot wire sealer, an induction sealer, an ultrasonic welder or sealer, or any suitable sealing apparatus and method.
In some embodiments, the fitment is sealed to the pouch immediately after the fitment is removed from the mold in which it is formed. In some such embodiments, the fitment is put onto and sealed to the pouch under a flow of sterile air and/or other gas, as discussed herein. Therefore, no contaminants can get onto the underside of the fitment that is sealed to the pouch. Thus, upon sealing to pouch, there are no contaminant and germs between the fitment and pouch.
In some embodiments, the fitment is sealed to the pouch while the fitment and/or the pouch is still hot, e.g., at a bactericidal temperature. Should there be any germs between the fitment and pouch, because the fitment and/or pouch are still hot, the heat will kill any germs at the interface of, or between, the fitment and pouch. In addition, or alternatively, the heating of the fitment and pouch material during thermal sealing of the fitment to the pouch will kill germs at the interface of, or between, the fitment and pouch.
In some embodiments, the single, continuous sealing interface is formed through application of heat or energy to an external surface of the fitment, without direct application of heat or energy to a surface of the pouch. In some such embodiments, the apparatus that applies the thermal or other energy to seal the fitment to the pouch contacts only external surfaces of the fitment, and does not touch the pouch surface. Sealing the fitment to the pouch in such manner helps avoid contamination of interior surfaces during the sealing process and/or potential damages to the pouch material due to the direct application of heat.
In some embodiments where the pouch is formed from a multi-layer material, the outer layer contains a material that bonds with the material of the fitment, and the inner layer does not contain a material that bonds with the material of the fitment. Accordingly, during thermal sealing of the fitment to the pouch, the fitment will not bond with the inner layer of the pouch. In some embodiments where the pouch is formed of a multi-layer material where an inner layer thereof defines a melting temperature higher than a melting temperature of the outer layer, the inner layer thus does not melt or soften when the outer layer is heated, and thus the inner layer does not seal together or bond with the fitment when heat is applied to seal the fitment to the pouch.
The fitment may be impulse sealed to the pouch using a suitable pressure, temperature, and duration. In some embodiments, the pressure, temperature, and duration of the impulse sealing may be the same pressure, temperature, and duration of the impulse sealing used to seal the edges of the film when forming the pouch as discussed above. As discussed above, the sealable portion of the fitment may, in some embodiments, be comprised of the same material as the pouch, and thus the same parameters and process for impulse sealing edges of the film can be used for impulse sealing the fitment to the pouch. The fitment is preferably sealed to the edge of the pouch, e.g., over the pouch aperture, that is formed when the blow molded film is flattened and folded, not on an edge of the pouch that is formed by heat sealing the open ends of the cylinder. This is because there is a risk that an intact seal cannot form on a heat-sealed seam, and a leak or hole could form.
As seen schematically in
The jaws 870, 872 effect a fluid-tight seal both laterally and apically. The interaction of the jaws 870, 872 and fitment 828 is shown, for example, in
When sealing the fitment to the pouch, in order to ensure sterility and no leaks, the portion of the fitment is sealed to the outer layer of the pouch everywhere around the periphery of the fitment/pouch interface. This is relatively easily achieved on flat parts of a pouch (e.g., the front and rear faces of the pouch) because there is ample mating surface on those parts between the fitment and the pouch. However, sealing is more difficult at the apical edge of the pouch where the material folds over the pouch from one side to the other (and where the fitment extends from one side of the pouch over the edge to the other side of the pouch), because there is less surface area contact between the fitment and the pouch. However, it is still necessary for a continuous single interface seal to extend from one side of the pouch to the other (over the apex of fold) to prevent leaks and contamination. This is accomplished in part by the interlocking configuration of the jaws 870, 872, which, as particularly shown in
In additional embodiments, a pouch aperture is formed on a first side of the pouch spaced from a marginal edge of the pouch. The fitment has first and second portions connected by a hinge, for example, a flexible or living hinge. The first portion of the fitment contains one or more ports extending therefrom. The one or more ports may have the configuration of one or more of the ports disclosed elsewhere herein. In some embodiments, the one or more ports have a first part extending transversely to the first portion and a second part extending from an outer end of the first part at so as to extend generally parallel to the first portion. A septum or valve is attached to an outer end of the second part to seal said outer end.
The fitment is sealed to the pouch such that the first portion is attached to the first side of the pouch and overlies the pouch aperture with the first part of the one or more parts in fluid communication with the pouch aperture, and the second portion overlies a second side of the pouch that is opposite the first side, the fitment being folded at its hinge so that the hinge is located substantially adjacent to the marginal portion located between the first and second sides. Substance may be filled and/or withdrawn from the pouch, e.g., in a sterile manner, through the one or more ports in a similar manner as in other embodiments described herein. In at least some such embodiments, the fitment is heat sealed to the pouch as described elsewhere herein to form a single, continuous interface between the fitment and the pouch.
One advantage of disclosed apparatuses and methods is that they can allow preventing the interior surfaces of the pouch or like container from being exposed to the ambient atmosphere from their formation during molding, through sterile or aseptic filling and storage, and preferably, through dispensing or withdrawal of the product from the interior chamber of the pouch or like container. Another advantage is that such surfaces can be sterile, particle free and pyrogen free from their formation during molding through sterile or aseptic filling and storage. As a result, the pouch or like container need not be sterilized prior to filling, such as by applying gamma radiation thereto, and need not be sterilized after filling, such as by applying terminal sterilization, in order to ensure the sterility of the product filled therein. However, such sterilization(s) nevertheless may be employed in connection with the disclosed apparatus and/or method, if so desired. Yet another advantage is that the illustrated septum (as further described in the above-mentioned co-pending patent applications incorporated herein) de-contaminates the closed needle or like injection member during penetration of the septum, and therefore the septum need not be surface sterilized or otherwise de-contaminated prior to closed needle or other closed injection member sterile or aseptic filling. A further advantage is that such sterile or aseptic filling may be performed in a non-classified environment while nevertheless providing for higher safety levels than products filled in sterile isolators.
Another advantage of the illustrated pouches is that a single interface seal is formed along the periphery of the pouch aperture between the base of the fitment and the pouch, thus providing for a high integrity and/or reliable seal, and obviating problems encountered in prior art pouches without single interface seals between the pouches and their fitments. Another advantage is that the fitment may include any desired number of ports, including one or two ports as illustrated herein, or another desired number of ports. In such embodiments, one port may be used to sterile or aseptically fill the interior of the pouch therethrough, and one or more other ports may be used to withdraw or dispense the sterile or aseptically filled product from the interior chamber(s) of the pouch. Another advantage is that any contamination of the sterile or aseptically filled product may be prevented from formulation of the product, through filling of the product into the pouch and withdrawal or dispensing of the product from the pouch, such as for administration of the product to a patient. A further advantage is that the pouch may be used to contain a hazardous or otherwise dangerous product or material, and the sealed pouch can prevent such a product from being exposed to the ambient environment, or the product or material may be withdrawn from the interior chamber of the pouch, as needed, through a sterile connector, such as one of the sterile connectors incorporated by reference below, connected to the port, or one of the ports, without exposing the product to the ambient environment.
The product filled within the pouch may be withdrawn from the interior chamber of the pouch through a sterile connector connected to the port or one of the ports of the fitment, and/or a product may be sterile or aseptically filled into the interior chamber of the pouch through a sterile connector connected to the port or one of the ports of the fitment. The sterile connectors usable with the disclosed pouches may take the form of any of the sterile connectors disclosed in any of the following patents or pending patent applications, which are hereby incorporated by reference in their entireties as part of the present disclosure: U.S. patent application Ser. No. 14/217,864, filed Mar. 18, 2014, entitled “Aseptic Connector with Deflectable Ring of Concern and Method,” which claims the benefit of similarly titled U.S. patent application Ser. No. 13/080,537, now U.S. Pat. No. 8,671,964, issued Mar. 18, 2014; entitled; U.S. patent application Ser. No. 14/536,566, filed Nov. 7, 2014, entitled “Device for Filling and Method,” which is a continuation in part of similarly titled U.S. patent application Ser. No. 13/874,839, filed May 1, 2013; U.S. patent application Ser. No. 13/864,919, filed Apr. 17, 2013, entitled “Self Closing Connector”; the U.S. patent application entitled “Single Use Connector,” filed Jan. 19, 2017, which claims the benefit of U.S. Provisional Patent Application No. 62/280,693, filed Jan. 19, 2016, entitled “Single Use Connectors.”
One advantage of the pouch and sterile connector is that they allow for closed transfer of product into or from the pouch without any exposure of the product to the ambient atmosphere throughout the transfer process. One advantage of such closed transfer processing is that it can obviate the need for cleaning in place (CIP) or sterilization in place (SIP) systems and processes. Yet another advantage of such closed transfer processing is that it can allow for a safer and improved quality product, such as products for intravenous (IV) administration. Products processed by such closed transfer processing can exhibit the lowest extractable levels, can be free of undesirable by-products, such as those degraded by heat during sterilization, and can be prevented from being subjected to heat degradation, such as may be encountered when products contact the relatively hot interior walls of recipient containers in connection with prior art blow form, fill and seal processing. As a result, the disclosed apparatus and methods can provide for higher safety levels for patients, for the products filled into and withdrawn from the pouches, for the medical professionals using the products filled into and withdrawn from the pouches, such as physicians, nurses, pharmacists, and other medical professionals, and for the ambient environment.
As may be recognized by those or ordinary skill in the pertinent art based on the teachings herein, numerous changes and modifications may be made to the above-described and other embodiments of the present invention without departing from its scope as defined, for example, in the appended claims. For example, the film used to make the pouch may include any number of layers made of any of numerous different materials that are currently known or that later become known. Similarly, the fitments may take any of numerous different configurations, may include any of numerous different parts or features, such as septa, sterile connectors, valves, and other devices for filling substances into the pouches, or withdrawing substances therefrom, may be made of any of numerous different materials or combinations of materials, and may include any of numerous different insert-molded, over-molded, co-molded, or other molded features, that are currently known, or that later become known. The invention may be used to make, or may be embodied in containers or devices other than pouches, such as vials, syringes, multiple dose delivery devices, or pouches that differ in shape and/or construction than those shown and described. In addition, steps of the disclosed methods may be eliminated, additional steps may be added, and/or steps may be performed in an order different from that described. The molding of the tubular film may be performed in line with, immediately prior to, and/or adjacent to, the molding of the fitments to the pouches, or the tubular film may be transported in a flattened, collapsed and/or rolled form, or the empty pouches may be transported, from a first location to a different or second location where the fitments are molded or attached to the pouches. The pouch apertures may take any of numerous different shapes and/or configurations, may be formed at any of numerous different locations, and/or may be formed any at time during the manufacturing process. The fitments and any components thereof may be made in accordance with any of numerous different molding processes or techniques that are currently known, or that later become known, such as insert molding and co-molding. Further, the molds used to form the fitments or any components thereof may take the form of any of numerous different types of molds that are currently known, or that later become known. Accordingly, this detailed description is to be taken in an illustrative as opposed to a limiting sense.
This patent application claims benefit under 35 U.S.C. §119 to U.S. provisional patent application Ser. No. 62/295,139, filed 14 Feb. 2016, U.S. provisional patent application Ser. No. 62/298,214, filed 22 Feb. 2016, and U.S. provisional patent application Ser. No. 62/323,561, filed 15 Apr. 2016, each of which is entitled “Pouch With Over-Molded Fitment And Method Of Making Same,” U.S. provisional patent application Ser. No. 62/280,700, filed 19 Jan. 2016, entitled “Pouch with Heat-Sealed External Fitment,” and U.S. provisional patent application Ser. No. 62/448,315, filed 19 Jan. 2017, entitled “Pouch With Fitment And Method Of Making Same,” all of which are hereby incorporated by reference in their entireties as part of the present disclosure.
| Number | Date | Country | |
|---|---|---|---|
| 62280700 | Jan 2016 | US | |
| 62295139 | Feb 2016 | US | |
| 62298214 | Feb 2016 | US | |
| 62323561 | Apr 2016 | US | |
| 62448315 | Jan 2017 | US |
