Medicament container systems with a plug and associated methods for aseptic medicament filling

Abstract

A closure system for containing a medicament is disclosed. The closure system includes a container that holds the medicament, a closure configured to seal an opening in the container, and a plug that contacts the closure and covers a hole formed in the closure, thereby sealing or reinforcing the closure. This system can ensure the secure containment of the medicament, prevent contamination, and maintain closure integrity. The closure system can be versatile, allowing for various types of medicaments and containers, while maintaining a consistent method for secure sealing.

Description

202400090-WGMEDICAMENT CONTAINER SYSTEMS WITH A PLUG AND ASSOCIATED METHODS FOR ASEPTIC MEDICAMENT FILLINGCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 772,843, filed March 17, 2025, the entirety of which is incorporated herein for any and all purposes.TECHNICAL FIELD

[0002] This disclosure is directed to container systems and methods, and more particularly for medicament container systems with a plug and associated methods for aseptic medicament filling and containment.BACKGROUND

[0003] Medicaments can be administered to patients using a number of different techniques, including for example by injection. Sterility is an important pre-requisite for medicaments, particularly for injectable medicaments such as small molecule pharmaceuticals, biologies, gene therapies, and cell therapies. Sterility of medicaments can directly impact the safety of patients as microbial contamination pre or post drug manufacturing can be detrimental for patient safety. Various techniques are available to meet sterility requirements for medicaments. For example, terminal sterilization can be used when medicaments are not sensitive to / not altered by sterilization processes. By contrast, aseptic fill / finish processes can be deployed when medicaments are sensitive to sterilization methods. Biologies along with gene and cell therapies are examples of medicaments that can be sensitive to sterilization methods and that accordingly can utilize aseptic fill / finish processes.

[0004] Aseptic fill / finish can involve the use of sterile ancillary materials, sterile equipment, and / or sterile environments. Based on factors including the stage of medicament development and scale of medicament manufacturing, aseptic fill / finish can involve a number of different processes. For example, aseptic fill / finish can involve manual filling: (a) in an open filling configuration where pipettes, biosafety cabinets and open containers can be used, (b) in a partially closed filling configuration where biosafety cabinets, open-ended filling equipment and closed containers can be used, or (c) in a closed filling configuration where closed filling equipment, closed containers and closed connector apparatuses can be used. Aseptic fill / finish202400090-WQ can involve semiautomated or fully-automatic filling including: (a) in an open filling configuration, where open containers can be filled aseptically in isolators or restricted access barrier systems (RABS), or (e) in a partially closed filling configuration where closed containers can be filled aseptically using open-ended filling equipment in isolators or RABS.SUMMARY

[0005] The use of closed containers introduces an additional layer of aseptic protection for the medicament. This can be particularly advantageous when the aseptic fill / finish process is not done in an isolator or RABS, commonly applicable to pre-pivotal clinical trials, autologous therapies, and rare disease indications. But current closed container systems have several drawbacks. Beyond sterilization of the closed container prior to filling, maintaining an aseptic environment inside the container throughout its life cycle can involve opening a passage in the container seal to enable filling of the medicament and re-establishing a seal after filling.Particular cell therapy formulations can involve more than one component and with more than one associated filling step, which can necessitate closed containers that are flexible between open-passage and closed positions. More generally, in order to support the medicament through its developmental life cycle, which typically involves manufacturing scale-up and automation, a closed container should be compatible with the variety of aseptic fill / finish configurations ranging from manual, single-dose throughput, open filling to fully automated, thousand-dose throughput, closed filling, and / or any of the configurations described previously.

[0006] These needs are met, in whole or in part, by the container systems and / or associated methods of this disclosure. Once aspect is directed to a closure system for containing a medicament. The closure system includes a container that is configured to contain the medicament and a closure that is configured to seal an opening of the container. The closure defines a hole extending therethrough. The closure system also includes a plug configured to contact the closure such that the plug covers the hole and blocks movement of liquid and gas into and out of the container through the hole.

[0007] Implementations may include one or more of the following features. The closure is made of an elastomer and the plug is made of an elastomer. The closure includes a coating on a surface configured to be contacted by the plug. At least one surface of the plug and at least one surface of the closure are surface treated. The closure system may include a cap that holds the closure on the container. The plug is integrated into the cap and is configured to contact the202400090-WQ closure when the cap is placed onto the container. The container is a vial that includes a flange, and the cap is configured to contact the flange when the cap is placed onto the vial, such that the cap is securely attached to the vial and the plug contacts the closure.

[0008] Another general aspect includes a closure system for containing a medicament. The closure system includes a container that is configured to contain the medicament and a closure that is configured to seal an opening of the container. The closure defines a recess. The closure system also includes a plug that is complimentary to the recess. The plug is configured to be fixed within the recess to seal or reinforce the closure.

[0009] Implementations may include one or more of the following features. The closure is made of an elastomer and the plug is made of an elastomer. At least one surface of the plug and at least one surface of the closure are surface treated. The closure defines a hole extending therethrough, and the plug is irremovably fixed to the closure within the recess to seal the hole. The closure system may include a cap that holds the closure on the container. The plug is fixed to the cap. The closure system further may include a cover that is removably attached to the cap and that covers an outer surface of the plug. The closure may include a first portion that is made of an elastomer and a second portion that is made of a plastic. The plug may include a first portion that is made of an elastomer and a second portion that is made of a plastic. The first portion of the plug, when the plug is fixed within the recess, interfaces with the first portion of the closure, and the second portion of the plug, when the plug is fixed to the closure within the recess, interfaces with the second portion of the closure. The first portion of the plug extends between an inner surface of the plug and an outer surface of the plug. The closure defines a hole extending therethrough, and the plug is irremovably fixed to the closure within the recess and to seal the hole. The plug is configured to be removably fixed to the closure within the recess. The closure defines a hole extending therethrough, and the plug, when removably fixed to the closure within the recess, seals the hole. The container is a vial. The container is a syringe, and the closure is a plunger configured to move within the syringe to eject the medicament from the syringe. The plunger may include a fastener configured to hold the plug within the recess. The closure system further may include a plunger rod, the plunger rod may include a connector, and the plug may include a connector that is configured to connect to connector of the plunger rod. The closure may include: an inner surface that faces an interior of the container when the closure seals the opening of the container; an outer surface that opposes the inner surface; an intermediate surface between the inner surface and the outer202400090-WG surface; and a sidewall surrounding the intermediate surface. The recess is recessed from the outer surface towards the inner surface and is defined by the intermediate surface and the sidewall.

[0010] Yet another general aspect includes a method of aseptically filling a container system. The method includes seating a closure within an opening of a container. The method also includes piercing the closure with a needle to define a hole through the closure. The method also includes filling the container with a medicament through the needle. The method also includes removing the needle from the hole. The method also includes sealing the hole with a plug that is fixed to a recess of the closure.

[0011] Implementations may include one or more of the following features. The method where sealing the hole may include irremovably fixing the plug to the closure within the recess. Sealing the hole may include removably fixing the plug to the closure within the recess.

[0012] Various additional features and advantages of this invention will become apparent to those of ordinary skill in the art upon review of the following detailed description of the illustrative embodiments taken in conjunction with the accompanying drawings.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0013] The following detailed description is better understood when read in conjunction with the appended drawings. For the purposes of illustration, examples are shown in the drawings; however, the subject matter is not limited to the specific elements and instrumentalities disclosed. In the drawings:

[0014] FIG. 1A illustrates a schematic, cross-section view of a container system according to a first embodiment of this disclosure before aseptic fill / finish.

[0015] FIG. IB illustrates a schematic, cross-section view of the first embodiment of the container system during aseptic filling with a medicament.

[0016] FIG. 1C illustrates a schematic, cross-section view of the first embodiment of the container system after needle removal.

[0017] FIG. ID illustrates a schematic, cross-section view of the first embodiment of the container system sealed with a plug.

[0018] FIG. IE illustrates a schematic, cross-section view of a sub-embodiment of the first embodiment of the container system after needle removal.202400090-WG

[0019] FIG. IF illustrates a schematic, cross-section view of the sub-embodiment of the first embodiment of the container system sealed with a plug.

[0020] FIG. 2A illustrates a schematic, cross-section view of a container system according to a second embodiment of this disclosure before aseptic fill / finish.

[0021] FIG. 2B illustrates a schematic, cross-section view of the second embodiment of the container system during aseptic filling with a medicament.

[0022] FIG. 2C illustrates a schematic, cross-section view of the second embodiment of the container system after needle removal.

[0023] FIG. 2D illustrates a schematic, cross-section view of the second embodiment of the container system sealed with a plug.

[0024] FIG. 2E illustrates a schematic, cross-section view of a sub-embodiment of the second embodiment of the container system after needle removal.

[0025] FIG. 2F illustrates a schematic, cross-section view of the sub-embodiment of the second embodiment of the container system sealed with a plug.

[0026] FIG. 3A illustrates a schematic, cross-section view of a container system according to a third embodiment of this disclosure before aseptic fill / finish.

[0027] FIG. 3B illustrates a schematic, cross-section view of the second embodiment of the container system during aseptic filling with a medicament.

[0028] FIG. 3C illustrates a schematic, cross-section view of the third embodiment of the container system after needle removal.

[0029] FIG. 3D illustrates a schematic, cross-section view of the third embodiment of the container system sealed with a plug.

[0030] FIG. 3E illustrates a schematic, cross-section view of a sub-embodiment of the third embodiment of the container system after needle removal.

[0031] FIG. 3F illustrates a schematic, cross-section view of the sub-embodiment of the third embodiment of the container system sealed with a plug.

[0032] FIG. 4 illustrates a process in accordance with aspects of this disclosure.

[0033] FIG. 5A illustrates a cross-section view a container system of a container system according to a fourth embodiment of this disclosure.202400090-WG

[0034] FIG. 5B illustrates a cross-section view of the fourth embodiment of the container system in another configuration.

[0035] FIG. 5C illustrates a cross-section view of a sub-embodiment of the fourth embodiment of the container system.

[0036] FIG. 5D illustrates a cross-section view of the sub-embodiment of the fourth embodiment of the container system in another configuration.

[0037] FIG. 5E illustrates a cross-section view of the sub-embodiment of the fourth embodiment of the container system in yet another configuration.DETAILED DESCRIPTION

[0038] As explained previously, aseptic fill / finish can involve the use of sterile ancillary materials, sterile equipment, and / or sterile environments. Based on factors including the stage of medicament development and scale of medicament manufacturing, aseptic fill / finish can involve a number of different processes. For example, aseptic fill / finish can involve manual filling: (a) in an open filling configuration where pipettes, biosafety cabinets and open containers can be used, (b) in a partially closed filling configuration where biosafety cabinets, open-ended filling equipment and closed containers can be used, or (c) in a closed filling configuration where closed filling equipment, closed containers and closed connector apparatuses can be used. Aseptic fill / finish can involve semiautomated or fully- automatic filling including: (a) in an open filling configuration, where open containers can be filled aseptically in isolators or restricted access barrier systems (RABS), or (e) in a partially closed filling configuration where closed containers can be filled aseptically using open-ended filling equipment in isolators or RABS. Categories of existing aseptic fill / finish systems include: (a) needle-based filling and laser-based sealing, (b) needle-less filling and heat-based sealing, (c) needle-less filling and radiation-free sealing.

[0039] A first existing aseptic fill / finish system has several key components including: a vial body, a vial stopper featuring a thermoplastic elastomeric septum, a vial seal, and a vial cap. The filling process for the first existing aseptic fill / finish system involves piercing the septum with a 13G needle using either a semi-automated benchtop apparatus or an automated robotic platform. Post-filling, the first existing aseptic fill / finish employs laser radiation to reseal the septum, thus re-establishing the closed environment. There is no definitive evidence on the202400090-WQ impact of laser radiation on cell viability or function, but the first existing aseptic fill / finish system has nevertheless been utilized in various cell therapy products.

[0040] However, there are notable limitations to the first existing aseptic fill / finish system. The fill / finish process is not entirely closed, as the filling needle is exposed prior to entering the vial, potentially increasing contamination risks. Additionally, the compatibility of the first existing aseptic fill / finish system is limited to specialized needles and filling equipment, which poses challenges for manual filling, particularly with viscous formulations that contain cryoprotective agents. The narrow passage of a 13G needle may also induce detrimental shear stress on therapeutic cells. Furthermore, the resealing mechanism necessitates the use of specialized laser equipment, introducing additional capital expenses and safety concerns within the fill / finish environment. These factors can complicate the adoption of the first existing aseptic fill / finish system in preclinical and early clinical settings. Moreover, inadvertent exposure of cells to laser radiation could have detrimental effects, underscoring the need for careful consideration in the application of this system.

[0041] A second existing aseptic fill / finish system aims to mitigate bioburden and particulate contamination while eliminating the need for radiation sterilization. The second existing aseptic fill / finish system includes a tubular vial body, with lengths of tubing extending from the top, each ending in a fill port and an air filter, and a foil-covered septum at the bottom for retrieval. The second existing aseptic fill / finish system can be analogous to traditional cryogenic bags used in various cell therapy applications, ensuring compatibility with established protocols.

[0042] Filling the second existing aseptic fill / finish system can be done through different methods, such as by piercing a needle through the elastomeric fill port or by utilizing a Luer-compatible connector for a needle-less approach. After filling, the second existing aseptic fill / finish system can be sealed by heat welding the tubing shut, re-establishing a closed environment to maintain sterility.

[0043] The second existing aseptic fill / finish system also has several limitations. For example, manual operations are often required to prepare and fill the container, which restricts scalability and automation potential. Although a semi-automated platform exists to manage controlled filling and sealing, manual intervention can still be necessary to ensure proper alignment of the vials. Additionally, the extensive use of ethylene vinyl acetate tubing in the second existing aseptic fill / finish system has been known to introduce particulates during cryogenic processing202400090-WQ and storage. Furthermore, the fill port and tubing connections can be prone to dislodgement, posing a risk to the sterility of the system.

[0044] A third existing aseptic fill / finish system is a vial-based container system that intends to facilitate a smooth transition between filling and sealing processes. The third existing aseptic fill / finish system also aims to minimize bioburden and particulates to ensure a sterile and safe environment for pharmaceutical products without the need for radiation. The third existing aseptic fill / finish system integrates a self-closing fill port with a vial seal and cap. The third existing aseptic fill / finish system incorporates a ring-shaped vial stopper with a hollow center, plug, and flange seal, that seamlessly connects the fill port to the vial body. The fill port itself features a valve assembly with a female outer structure and a mobile central piece.

[0045] When the third existing aseptic fill / finish system is filled, the vial remains securely closed until a syringe or compatible fill line with a matching male end is connected. This action depresses the central valve, creating an open passage for fluid flow. Upon disconnection, the center valve automatically returns to its resting position, effectively resealing the vial. This ensures that the vial remains closed without relying on radiation or causing damage to the container material. Furthermore, the fill port can also serve as a retrieval port for administering the drug product.

[0046] The third existing aseptic fill / finish system also has limitations. The junction between the mobile flexible central piece and the surrounding rigid structure is exposed when the vial is closed, posing a potential contamination risk during the movement of the central piece or while undergoing thermomechanical stresses in low-temperature or cryogenic conditions.Additionally, the valve is specifically designed for use with syringe or Luer-ended filling systems and is not compatible with needle-based methods.

[0047] Aspects of this disclosure are directed to closure systems, container systems, and methods for aseptic fill / finish that, in whole or in part, address the aforementioned deficiencies of existing aseptic fill / finish systems. In one aspect of this disclosure, a closure system includes a container that can contain medicament and a closure that is configured to seal an opening of the container. The closure defines a recess. The closure system further includes a plug that is complimentary to the recess. The plug is configured to be fixed within the recess to seal or reinforce the closure.

[0048] The container can be of any form factor that has space for placing the closures described herein. The closure can include two parts: the first part (hereinafter “filling closure”)202400090-WQ can be a thin flange serum stopper, which can define a small injection hole. In some aspects, the flange serum stopper can be manufactured with the small injection hole. Alternatively, the hole can be made by a filling needle when the container is filled. Tn embodiments, the hole can have an inner diameter slightly wider than the outer diameter of the filling needle. The outer surface of the filling closure can be covered with an over-molded film that can prevent microbial ingress and maintain the sterility of the vial. The over-molded film may cover the entire surface of the filling closure or a part of the surface. In embodiments where the hole is made by the injection needle during filling, the over-molded film may be punctured by the filling needle as the filling needle punctures the filling closure.

[0049] The second part of the closure (hereinafter "plug") can be separate from the first part. In some embodiments, the plug can include an elastomer or another suitable polymer. In specific embodiments, the plug may be a flat elastomeric sheet or disc. The plug can be preassembled inside an aluminum or plastic seal or in a fixture similar to a cap. The plug can be either flat or can contain a protrusion aligned with the hole of the filling closure. This protrusion can ensure plugging of the hole to ensure sealing / closure post filling.

[0050] During drug dispensing, the filling nozzle can rupture the over-molded film in the filling closure (or can pierce the filing closure to form the hole) and fill the vial through the filling hole. Post filling, the plug can be either manually or automatically (e.g., using a robotic arm) placed on top of the filling closure and sealed by either crimping (for example, in the case of an aluminum seal) or by a press-fit mechanism (for example, with a plastic seal or cap-like fixture).

[0051] The interaction and compression between the surfaces of the plug and the filling closure can form a seal that will not allow for any significant transition of gases or fluids into or out of the vial. This would enable the supply of a closed sterile container to end users, which can then be utilized in a closed filling process. The container closure systems of this disclosure can be scalable, meaning that they can be filled manually and scaled through semi-automated and fully automated filling equipment. The closure systems, container systems, and methods for aseptic fill / fmish of this disclosure can be used in both vacuum and non-vacuum environments.

[0052] The container systems and methods for aseptic fill / fmish of aspects of this disclosure can function effectively in both low-scale manual handling within biosafety cabinets or laboratory environments, as well as in high-throughput filling lines. During the filling process, the hypodermic needle can fill the vial while simultaneously venting the air inside. The next202400090-WG step can involve the filling machine plugging the hole in the filling closure to create a permanent seal. This system can ensure sterility is maintained throughout a shelf life of the medicament and can provide easy access to the vial septum.

[0053] The closure systems, container systems, and methods for aseptic fill / finish can be suitable for cryogenic storage of cell and gene therapies. The seal resulting from the plugging of the closure systems can provide container closure integrity throughout freeze / thaw cycles. For example, the seal formed by closure systems, container systems, and methods for aseptic fill / finish can prevent fluid communication through the hole at ultra cold temperatures, cryogenic temperatures, room temperatures, and temperatures above room temperature. For example, the seal formed by closure systems, container systems, and methods for aseptic fill / finish can prevent fluid communication through the hole at temperatures below -180°C, temperatures between -180°C and -80°C, inclusive (i.e., including both endpoints of the range), temperatures between -80°C and 30°C, inclusive, and / or at temperatures above 30°C.

[0054] Aspects of the closure systems, container systems, and methods for aseptic fill / finish can provide a closed filling solution for high-value medicaments (e.g., cell therapies), overcoming the limitations of current containment solutions and presenting a superior storage option. The closure systems, container systems, and methods for aseptic fill / finish can used with International Organization for Standardization-dimensioned vials and / or syringes, which can ensure compatibility with existing downstream infrastructure, such as nests, tubs, racks, and freezers. These and other aspects of this disclosure are shown in FIG. 1 A through FIG. 5E of this disclose and are described as follows.

[0055] FIG. 1 A through FIG. IF show aspects of a container system 100 of this disclosure. FIG. 1A shows a cross-section view of the container system 100 prior to aseptic fill / finish. The container system 100 can include a container 102 with an opening 104. The container 102 can be any structure that can contain medicament such as a vial, a syringe, a bottle, an ampule, among other possibilities. The container 102 can be formed of glass, plastic (e.g., cyclic olefin copolymer, cyclic olefin polymer), among other possibilities. In embodiments, the container 102 can include a flange 106 adjacent to (e.g., surrounding) the opening 104.

[0056] The container system 100 can include a closure 108, which can be received within the opening 104. The closure 108 can be structured and arranged to seal the opening 104. In embodiments, the closure 108 can be a stopper, a plunger, a cap, among other possibilities. The closure 108 can be formed of elastomer, plastic, combinations thereof, among other202400090-WG possibilities. It should be understood that the closure 108 can include any suitable material and dimensions such that the opening 104 is sufficiently sealed during expected use (i.e., filling, storage, freezing, thawing, transportation, etc.) In embodiments, the closure 108 can be a unitary body formed substantially or entirely of an elastomer, though other materials are possible. The closure 108 can include an inner surface 108a. When the closure 108 is seated within the opening 104 to seal the opening 104, the inner surface 108a can face the interior of the container 102. Accordingly, medicament within the container 102 can be exposed to the inner surface 108a. In some embodiments, the inner surface 108a can be coated with one or more coatings or laminations to protect the medicament from potential contamination associated with the material forming the closure 108. The coatings or laminations may include fluoropolymers or non-fluorinated materials.

[0057] The closure 108 can include an outer surface 108b, which can oppose the inner surface 108a and / or face away from the inner surface 108a. The closure 108 can further include an intermediate surface 108c between the inner surface 108a and the outer surface 108b and one or more sidewalls 108d. The sidewalls 108d can partially or completely surround the intermediate surface 108c. The intermediate surface 108c and the sidewalls 108d can together define a recess 110. The recess 110 can be recessed inwardly from the outer surface 108b towards the inner surface 108a.

[0058] FIG. IB shows a cross-section view of the container system 100 during aseptic filling with a medicament. The closure 108 can be pierced by a needle 112. The needle 112 can be inserted into the recess 110 and can puncture through the intermediate surface 108c and the inner surface 108a of the closure 108 to provide access to the interior of the container 102. Medicament can be aseptically transferred into the container 102 from a fill system 114 via the needle 112.

[0059] FIG. 1C shows a cross-section view of the container system 100 after the container is filled with medicament and after the needle 112 is removed. As a result of the needle 112 puncturing the closure 108 during the aseptic filling with the medicament, the closure 108 can define a hole 116. Alternatively, in embodiments the hole 116 can be formed in the closure 108 by a means other than the needle 112, such as when the closure 108 is molded. This can be advantageous in that it can be easier for the needle 112 to be inserted through the closure 108 via a hole 116 that is preformed. In such embodiments in which the hole 116 is formed before insertion of the needle 112, the outer surface 108b of the closure 108 can include a coating,202400090-WQ lamination, or film to preserve sterility of the inside of the container 102 before aseptic filling, and the coating, lamination, or film can be punctured by the needle 112 during filing.

[0060] The hole 116 can extend through closure 108 between the intermediate surface 108c and the inner surface 108a. For example, the hole 116 can include a first opening 116a at the inner surface 108a and a second opening 116b at the intermediate surface 108c. The hole 116 can provide a pathway for fluid communication between the interior of the container 102 and an external environment surrounding the container system 100. In embodiments, the closure 108 can be formed of a material (e.g., an elastomer) that is self-sealing. As a result, the hole 116 can be completely or partially collapsed between the first opening 116a and the second opening 116b. Alternatively, the hole 116 can be partially or completely open between the first opening 116a and the second opening 116b.

[0061] Since the hole 116 can provide a pathway for fluid communication, the hole 116 can compromise container closure integrity (e.g., the seal) of the container system 100, particularly when the container system 100 is subject to temperature fluctuations. Accordingly, the container system 100 can include a plug 118 that can seal or reinforce the closure 108 to maintain container closure integrity at a wide range of temperatures. The plug 118 can be structured and arranged to seal the hole 116. The plug 118 can be complimentary to the recess 110 such that the plug 118 can be at least partially received within the recess 110 to seal the hole 116. The plug 118 can have a size and a shape that at least partially corresponds to a size and a shape of the recess 110. For example, the plug 118 can have a male conical frustrum shape and the recess 110 can have a complimentary female conical frustrum shape, though other shapes are possible.

[0062] A size of the plug 118 can be greater than or equal to a size of the recess 110.According to this configuration, the plug 118 can interface with the recess 110 to seal or reinforce the closure 108. For example, the plug 118 can include an inner surface 118a and an outer surface 118b that can oppose and / or face away from the inner surface 118a. The plug 118 can further include one or more sidewalls 118c, which can partially or completely surround the inner surface 118a and the outer surface 118b. When the closure 108 is received within the recess 110, the inner surface 118a can directly interface with some or all of the intermediate surface 108c to seal the hole 116. Moreover, when the closure 108 is received within the recess 110, the sidewalls 118c can directly interface with some or all of the sidewalls 108d to further reinforce or seal the closure 108. In embodiments, some or all of these interfacing surfaces can202400090-WG be surface treated, which can improve the seal between plug 118 and the closure 108 when the plug 118 is received within the recess 110. The surface treatments can include plasma treatments, chemical primer or adhesive treatments, surface roughening, silane coupling agent treatments, corona treatments, ultraviol et / ozone treatments, among other possibilities. Any or all of surfaces of the closure 108 and of the plug 118 can be surface treated, including the intermediate surface 108c, the sidewalls 108d, the inner surface 118a, and / or the sidewalls 118c.

[0063] The plug 118 can be formed of elastomer, plastic, combinations thereof, among other possibilities. In embodiments, the plug 118 can be a unitary body formed of elastomer. The elastomer the forms the plug 118 can be of the same type or of a different type than the elastomer that forms the closure 108.

[0064] In embodiments, the inner surface 118a can include one or more protrusions. The plug 118 and the recess 110 can be structured and arranged such that, when the plug 118 is received within the recess 110, the protrusion projecting from the inner surface 118a can enter the second opening 116b of the hole 116 to seal the hole 116. Alternatively, the inner surface 118a can be substantially flat with no protrusions.

[0065] In embodiments, the plug 118 can be sized such that, when the plug 118 is received within the recess 110, the outer surface 118b of the plug 118 can be flush with the outer surface 108b of the closure 108. This can be advantageous in that a cap 120, such as standard crimp cap, can be applied to the closure 108 and the plug 118 to apply pressure to the closure 108 and the plug 118 and further improve the seal and container closure integrity of the container system 100. Alternatively, the plug 118 can be sized such that, when the plug 118 is received within the recess 110, the outer surface 118b of the plug 118 can project outwardly beyond the outer surface 108b of the closure 108. This can be advantageous in that when a cap 120 is connected to the flange 106 of the container 102, pressure applied by the cap 120 can be concentrated at the plug 118, which can compress the plug 118 and improve the seal and container closure integrity of the container system 100.

[0066] FIG. ID shows a cross-section view of the container system 100 with the plug 118 received within the recess 110 to reinforce or seal the closure 108. Because the plug 118 is complementary with the recess 110, the plug 118 can fit within the recess 110 and can seal the hole 116.202400090-WG

[0067] In embodiments, the plug 118 can be irremovably fixed within the recess 110 to seal the hole 116. For example, the plug 118 can be heat fused (e.g., laser welded) to the closure 108, adhered to the closure 108 with an adhesive, doped with nanoparticles for thermal expansion and subsequent bonding to the closure 108, snap fit to the closure 108, among other possibilities. Additionally or alternatively, the cap 120 (e.g., crimp cap) can fix the plug 118 within the recess 110 to reinforce or seal the closure 108. Nevertheless, in embodiments the cap 120 can be optional and the plug 118 can be fixed (e g., irremovably fixed) to the closure 108 via any of the previously described techniques. The plug 118, when fixed within the recess 110 with or without the cap 120, can reinforce or seal the closure 108 to provide container closure integrity throughout a wide range of temperatures including temperatures below -180°C, temperatures between -180°C and -80°C, inclusive (e.g., including the endpoints of the range), temperatures between -80°C and 30°C, inclusive, and / or at temperatures above 30°C.

[0068] FIG. IE and FIG. IF show cross-section views of a sub-embodiment of the container system 100. The sub-embodiment of the container system 100 can include each of the aspects, features, relationships, etc., described previously with respect to the container system 100. For sub-embodiment of the container system 100, the plug 118 can be integrated into the cap 120. FIG. IE is cross-section view of the sub-embodiment of the container system 100 after removal of the needle 112 and is analogous to the view the embodiment shown in FIG. 1C.

[0069] FIG. IF is a cross-section view of the sub-embodiment of the container system 100 with the plug 118 received within the recess 110 to reinforce or seal the closure 108. In embodiments, the cap 120 can be the sole means for fixing the plug 118 within the recess 110. This can be advantageous in that it can simplify the sealing of the hole 116. In alternative embodiments, the plug 118 can be fixed to the closure 108 within the recess 110 using any of the previously discussed techniques in addition to the cap 120.

[0070] In embodiments, the sub-embodiment of the container system 100 can include a cover 122. The cover 122 can cover the outer surface 118b of the plug 118. The cover 122 can be removable from the cap 120 to expose the outer surface 118b. This can be advantageous in that the exposed outer surface 118b can be more readily punctured during medicament administration. The cover 122 can be made of plastic, though other materials are possible.

[0071] FIG. 2A through FIG. 2F show aspects of another container system 200 of this disclosure. FIG. 2A shows a cross-section view of the container system 200 prior to aseptic fill / finish. The container system 200 can include aspects, features, relationships, etc., of the202400090-WQ container system 100, and vice versa. For example, the container system 200 can include a container 202 with an opening 204. The container 202 can be any structure that can contain medicament such as a vial, a syringe, a bottle, an ampule, among other possibilities. The container 202 can be formed of glass, plastic (e.g., cyclic olefin copolymer, cyclic olefin polymer), among other possibilities. In embodiments, the container 202 can include a flange 206 adjacent to (e.g., surrounding) the opening 204.

[0072] The container system 200 can include a closure 208, which can be received within the opening 204. The closure 208 can be structured and arranged to seal the opening 204. In embodiments, the closure 208 can be a stopper, a plunger, a cap, among other possibilities. The closure 208 can include an inner surface 208a. When the closure 208 is seated within the opening 204 to seal the opening 204, the inner surface 208a can face the interior of the container 202. Accordingly, medicament within the container 202 can be exposed to the inner surface 208a. In embodiments, the inner surface 208a can be coated with a barrier film (e.g., ETFE) to protect the medicament from potential contamination associated with the material forming the closure 208.

[0073] The closure 208 can include an outer surface 208b, which can oppose the inner surface 208a and / or face away from the inner surface 208a. The closure 208 can further include an intermediate surface 208c between the inner surface 208a and the outer surface 208b and one or more sidewalls 208d. The sidewalls 208d can partially or completely surround the intermediate surface 208c. The intermediate surface 208c and the sidewalls 208d can together define a recess 210. The recess 210 can be recessed inwardly from the outer surface 208b towards the inner surface 208a.

[0074] The closure 208 can be formed of elastomer, plastic, combinations thereof, among other possibilities. For example, the closure 208 can include a first portion 208e formed of a first material and a second portion 208f formed of a second material that is different from the first material. The first material can be an elastomer, though other materials are possible. The second material can a plastic, though other materials are possible. The first portion 208e can be an insert within the second portion 208f. For example, the first portion 208e can be embedded within and / or surrounded by the second portion 208f. The second portion 208f can interface directly with the closure 208 at the opening 204 of the container 202. For example, the second portion 208f can be received within the opening 204 of the container 202. The first portion 208e can define a bottom of the recess 210. For example, some or all of the intermediate202400090-WG surface 208c that defines part of the recess 210 can be an outer surface of the first portion 208e. A portion of the inner surface 208a can be an inner surface of the first portion 208e while the remainder of the inner surface 208a and be an inner surface of the second portion 208f. Some or all of the sidewalls 208d can be walls of the second portion 208f. The outer surface 208b can be an outer surface of the second portion 208f.

[0075] FIG. 2B shows a cross-section view of the container system 200 during aseptic filling with a medicament. The closure 208 can be pierced by a needle 212. The needle 212 can be inserted into the recess 210 and can puncture the first portion 208e, through the intermediate surface 208c and the inner surface 208a, to provide access to the interior of the container 202. Medicament can be aseptically transferred into the container 202 from a fill system 214 via the needle 212.

[0076] FIG. 2C shows a cross-section view of the container system 200 after the container is filled with medicament and after the needle 212 is removed. As a result of the needle 212 puncturing the first portion 208e during the aseptic filling with the medicament, the closure 208 can define a hole 216. Alternatively, the hole 216 can be preformed before the needle 212 is inserted and the closure 208 can include a barrier film puncturable by the needle 212, as previously described.

[0077] The hole 216 can extend through the first portion 208e between the intermediate surface 208c and the inner surface 208a. For example, the hole 216 can include a first opening 216a at the inner surface 208a of the first portion 208e and a second opening 216b at the intermediate surface 208c. The hole 216 can provide a pathway for fluid communication between the interior of the container 202 and an external environment surrounding the container system 200. In embodiments, the first portion 208e can be formed of a material (e.g., an elastomer) that is self-sealing. As a result, the hole 216 can be completely or partially collapsed between the first opening 216a and the second opening 216b. Alternatively, the hole 216 can be partially or completely open between the first opening 216a and the second opening 216b.

[0078] Since the hole 216 can provide a pathway for fluid communication, the hole 216 can compromise container closure integrity (e.g., the seal) of the container system 200, particularly when the container system 200 is subject to temperature fluctuations. The container system 200 can thus include a plug 218 that can seal or reinforce the closure 208 to maintain container closure integrity at a wide range of temperatures. The plug 218 can be structured and arranged202400090-WQ to seal the hole 216. The plug 218 can be complimentary to the recess 210 such that the plug 218 can be at least partially received within the recess 210 to seal the hole 216. The plug 218 can have a size and a shape that at least partially corresponds to a size and a shape of the recess 210. For example, the plug 218 can have a male conical frustum shape and the recess 210 can have a complementary female conical frustum shape, though other shapes are possible.

[0079] A size of the plug 218 can be greater than or equal to a size of the recess 210.According to this configuration, the plug 218 can interface with the recess 210 to seal or reinforce the closure 208. For example, the plug 218 can include an inner surface 218a and an outer surface 218b that can oppose and / or face away from the inner surface 218a. The plug 218 can further include one or more sidewalls 218c, which can partially or completely surround the inner surface 218a and the outer surface 218b.

[0080] The plug 218 can be formed of elastomer, plastic, combinations thereof, among other possibilities. In embodiments, the plug 118 can be a composite body with a first portion 218d and a second portion 218e that are formed of different materials. For example, the first portion 218d can be formed of an elastomer, though other materials are possible. The elastomer that forms the first portion 218d can be of the same type or of a different type from the elastomer that forms the first portion 208e of the closure 208. The second portion 218e can be formed of a plastic, that other materials are possible. The plastic that forms the second portion 218e can be the of the same type or of a different type from the plastic that forms the second portion 208f of the closure 208. The first portion 218d can define central portion of the plug 218 and the second portion 218e can define an outer portion of the plug 218. The first portion 218d can include the inner surface 218a and the outer surface 218b and can extend between the inner surface 218a and the outer surface 218b. The second portion 218e can include the sidewalls 218c.

[0081] When the closure 208 is received within the recess 210, the inner surface 218a can directly interface with some or all of the intermediate surface 208c to seal the hole 216. For example, the first portion 218d (e.g., the inner surface 218a) of the plug 218 can directly interface with the first portion 208e (e.g., the intermediate surface 208c). Since the first portion 218d of the plug 218 and the first portion 208e of the closure 208 can be formed of the same or similar materials (e.g., elastomer), the seal formed by the direct interface between these structures can be improved.202400090-WG

[0082] When the closure 208 is received within the recess 210, the sidewalls 218c can directly interface with some or all of the sidewalls 208d to further reinforce or seal the closure 208. For example, the second portion 218e (e.g., the sidewalls 218c) of the plug 218 can directly interface with some or all of the second portion 208f (e.g., the sidewalls 208d) of the closure 208. Since the second portion 218e of the plug 218 and the second portion 208f of the closure 208 can be formed of the same or similar materials (e.g., plastic), the seal formed by the direct interface between these structures can be improved.

[0083] In embodiments, some or all of these interfacing surfaces can be surface-treated, which can improve the seal between plug 218 and the closure 208 when the plug 218 is received within the recess 210. The surface treatments can include plasma treatments, chemical primer or adhesive treatments, surface roughening, silane coupling agent treatments, corona treatments, ultraviol et / ozone treatments, among other possibilities. Any or all of surfaces of the closure 208 and of the plug 218 can be surface-treated, including the intermediate surface 208c, the sidewalls 208d, the inner surface 218a, and / or the sidewalls 218c.

[0084] In embodiments, the inner surface 218a can include one or more protrusions. The plug 218 and the recess 210 can be structured and arranged such that, when the plug 218 is received within the recess 210, the protrusion projecting from the inner surface 218a can enter the second opening 216b of the hole 216 to seal the hole 216. Alternatively, the inner surface 218a can be substantially flat with no protrusions.

[0085] In embodiments, the plug 218 can be sized such that, when the plug 218 is received within the recess 210, the outer surface 218b of the plug 218 can be flush with the outer surface 208b of the closure 208. This can be advantageous in that a cap 220, such as standard crimp cap, can be applied to the closure 208 and the plug 218 to apply pressure to the closure 208 and the plug 218 and further improve the seal and container closure integrity of the container system 200. Alternatively, the plug 218 can be sized such that, when the plug 218 is received within the recess 210, the outer surface 218b of the plug 218 can project outwardly beyond the outer surface 208b of the closure 208. This can be advantageous in that when the cap 220 is connected to the flange 206 of the container 202, pressure applied by the cap 220 can be concentrated at the plug 218, which can compress the plug 218 and improve the seal and container closure integrity of the container system 200.

[0086] FIG. 2D shows a cross-section view of the container system 200 with the plug 218 received within the recess 210 to reinforce or seal the closure 208. Because the plug 218 is202400090-WG complementary with the recess 210, the plug 218 can fit within the recess 210 and can seal the hole 216.

[0087] In embodiments, the plug 218 can be irremovably fixed within the recess 210 to seal the hole 216. For example, the plug 218 can be heat fused (e.g., laser welded) to the closure 208, adhered to the closure 208 with an adhesive, doped with nanoparticles for thermal expansion and subsequent bonding to the closure 208, snap fit to the closure 208, among other possibilities. Additionally or alternatively, the cap 220 (e.g., crimp cap) can fix the plug 218 within the recess 210 to reinforce or seal the closure 208. Nevertheless, in embodiments the cap 220 can be optional and the plug 218 can be fixed (e g., irremovably fixed) to the closure 208 via any of the previously described techniques. The plug 218, when fixed within the recess 210 with or without the cap 220, can reinforce or seal the closure 208 to provide container closure integrity throughout a wide range of temperatures including temperatures below -180°C, temperatures between -180°C and -80°C, inclusive (e.g., including the endpoints of the range), temperatures between -80°C and 30°C, inclusive, and / or at temperatures above 30°C.

[0088] FIG. 2E and FIG. 2F show cross-section views of a sub-embodiment of the container system 200. FIG. 2E is a cross-section view of the sub-embodiment of the container system 200 after removal of the needle 212 and is analogous to the view of the embodiment shown in FIG. 2C. The sub-embodiment of the container system 200 can include the aspects, features, relationships, etc., described previously in reference to the container system 200, and vice versa. The sub-embodiment of the container system 200 can include an alternate plug 224. The alternate plug 224 can be unitary and can be formed entirely or substantially of the same material (e.g., plastic). The alternate plug 224 can be removably attached to the closure 208. This can be advantageous for administration of medicament, since removal of the alternate plug 224 can provide access to the first portion 208e of the closure 208, which can be formed of a material (e.g., an elastomer) that is more easily puncturable than the alternate plug 224. For example, the alternate plug 224 can include threads 226 and the closure 208 can include complimentary threads 228 such that the alternate plug 224 can be threaded into the recess 210 of the closure 208. Alternative means for removably fixing the alternate plug 224 to the closure 208 are possible such as press fitting, snap fitting, among other possibilities. Additionally though other embodiments of container systems (e.g., container system 100, container system 200, etc.) described herein are disclosed with plugs irremovably fixed to respective closures, it is to be understood that alternative embodiments of any such container systems can be202400090-WG removably fixed in any of the manners described in reference to this sub-embodiment of the container system 200.

[0089] FIG. 2F is a cross-section view of the sub-embodiment of the container system 200 with the alternate plug 224 threaded into the recess 210 to reinforce or seal the closure 208. In embodiments, the cap 220 can be provided to hold the closure 208 to the container 202. For example, the cap 220 can be crimped onto the flange 206 of the container 202 to hold the closure 208 to the container 202. In embodiments, the cap 220 can include an opening 221 and the alternate plug 224 can project out of the opening 221. This can be advantageous in that the alternate plug 224 can be gripped and removed to provide access to the first portion 208e of the closure 208 without removing the cap 220. Alternatively, the sub-embodiment of the container system 200 can be provided without a cap 220.

[0090] FIG. 3A through FIG. 3F show aspects of another container system 300 of this disclosure. FIG. 3A shows a cross-section view of the container system 300 prior to aseptic fill / finish. The container system 300 can include aspects, features, relationships, etc., of the container system 100 or the container system 200, and vice versa. For example, the container system 300 can include a syringe 302. The syringe 302 can be formed of glass, plastic (e.g., cyclic olefin copolymer, cyclic olefin polymer), among other possibilities. The syringe 302 can include a proximal opening 304 and a distal opening 303. The container system 300 can include a cap 305 that can be removably attached to the distal opening 303 to seal the distal opening 303. In embodiments, the syringe 302 can include a flange 306 adjacent to (e.g., surrounding) the proximal opening 304.

[0091] The container system 300 can include a plunger 308, which can be received within the syringe 302. The plunger 308 can be structured and arranged to seal the syringe 302 between the cap 305 and the plunger 308. The plunger 308 can include an inner surface 308a. When the plunger 308 is arranged within the syringe 302, the inner surface 308a can face the distal opening 303. Medicament within the syringe 302 can be exposed to the inner surface 308a. In embodiments, the inner surface 308a can be coated with a barrier film (e.g., ETFE) to protect the medicament from potential contamination associated with the material forming the plunger 308.

[0092] The plunger 308 can include fasteners 308b (e.g., tabs, arms, projections, combinations thereof, among other possibilities), which can oppose the inner surface 308a and / or face away from the inner surface 308a. The plunger 308 can further include an intermediate surface 308c202400090-WG between the inner surface 308a and the fasteners 308b and one or more sidewalls 308d. The sidewalls 308d can partially or completely surround the intermediate surface 308c. The fasteners 308b, the intermediate surface 308c and the sidewalls 308d can together define a recess 310. The plunger 308 can be formed of elastomer, plastic, combinations thereof, among other possibilities.

[0093] FIG. 3B shows a cross-section view of the container system 300 during aseptic filling with a medicament. The plunger 308 can be pierced by a needle 312. The needle 312 can be inserted into the recess 310 and can puncture the plunger 308, through the intermediate surface 308c and the inner surface 308a, to provide access to the interior of the syringe 302.Medicament can be aseptically transferred into the syringe 302 from a fill system 314 via the needle 312.

[0094] FIG. 3C shows a cross-section view of the container system 300 after the container is filled with medicament and after the needle 312 is removed. As a result of the needle 312 puncturing the plunger 308 during the aseptic filling with the medicament, the plunger 308 can define a hole 316. Alternatively, the hole 316 can be preformed before the needle 312 is inserted and the plunger 308 can include a barrier film puncturable by the needle 312, as previously described.

[0095] The hole 316 can extend through the plunger 308 between the intermediate surface 308c and the inner surface 308a. For example, the hole 316 can include a first opening 316a at the inner surface 308a and a second opening 316b at the intermediate surface 308c. The hole 316 can provide a pathway for fluid communication between the interior of the syringe 302 and an external environment (via the proximal opening 304) surrounding the container system 300. In embodiments, the plunger 308 can be formed of a material (e.g., an elastomer) that is selfsealing. As a result, the hole 316 can be completely or partially collapsed between the first opening 316a and the second opening 316b. Alternatively, the hole 316 can be partially or completely open between the first opening 316a and the second opening 316b.

[0096] Since the hole 316 can provide a pathway for fluid communication, the hole 316 can compromise container closure integrity (e.g., the seal) of the container system 300, particularly when the container system 300 is subject to temperature fluctuations. The container system 300 can thus include a plug 318 that can seal or reinforce the plunger 308 to maintain container closure integrity at a wide range of temperatures. The plug 318 can be structured and arranged to seal the hole 316. The plug 318 can be complimentary to the recess 310 such that the plug202400090-WG 318 can be partially or completely received within the recess 310 to seal the hole 316. The fasteners 308b of the plunger 308 can hold the plug 318 within the recess 310. The plug 318 can have a size and a shape that at least partially corresponds to a size and a shape of the recess 310. For example, the plug 318 can have a cylindrical shape and the recess 310 can have a complementary cylindrical shape, though other shapes are possible. A size of the plug 318 can be greater than or equal to a size of the recess 310. According to this configuration, the plug 318 can interface with the recess 310 to seal or reinforce the plunger 308. For example, the plug 318 can include an inner surface 318a and an outer surface 318b that can oppose and / or face away from the inner surface 318a. The plug 318 can further include one or more sidewalls 318c, which can partially or completely surround the inner surface 318a and the outer surface 318b. The plug 318 can be formed of elastomer, plastic, combinations thereof, among other possibilities.

[0097] When the plunger 308 is received within the recess 310, the inner surface 318a can directly interface with some or all of the intermediate surface 308c to seal the hole 316. When the plunger 308 is received within the recess 310, the sidewalls 318c can directly interface with some or all of the sidewalls 308d to further reinforce or seal the plunger 308. In embodiments, some or all of these interfacing surfaces can be surface-treated, which can improve the seal between plug 318 and the plunger 308 when the plug 318 is received within the recess 310. The surface treatments can include plasma treatments, chemical primer or adhesive treatments, surface roughening, silane coupling agent treatments, corona treatments, ultraviolet / ozone treatments, among other possibilities. Any or all of surfaces of the plunger 308 and of the plug 318 can be surface-treated, including the intermediate surface 308c, the sidewalls 308d, the inner surface 318a, and / or the sidewalls 318c.

[0098] In embodiments, the inner surface 318a can include one or more protrusions. The plug 318 and the recess 310 can be structured and arranged such that, when the plug 318 is received within the recess 310, the protrusion projecting from the inner surface 318a can enter the second opening 316b of the hole 316 to seal the hole 316. Alternatively, the inner surface 318a can be substantially flat with no protrusions.

[0099] FIG. 3D shows a cross-section view of the container system 300 with the plug 318 received within the recess 310 (and held by the fasteners 308b) to reinforce or seal the plunger 308. Because the plug 318 is complementary with the recess 310, the plug 318 can fit within the recess 310 and can seal the hole 316. In embodiments, the plug 318 can be irremovably202400090-WG fixed within the recess 310 to seal the hole 316. For example, the plug 318 can be heat fused (e.g., laser welded) to the plunger 308, adhered to the plunger 308 with an adhesive, doped with nanoparticles for thermal expansion and subsequent bonding to the plunger 308, snap fit to the plunger 308, among other possibilities. The plug 318, when fixed within the recess 310, can reinforce or seal the plunger 308 to provide container closure integrity throughout a wide range of temperatures including temperatures below -180°C, temperatures between -180°C and -80°C, inclusive (e.g., including the endpoints of the range), temperatures between -80°C and 30°C, inclusive, and / or at temperatures above 30°C.

[0100] FIG. 3E and FIG. 3F show cross-section views of a sub-embodiment of the container system 300. FIG. 3E is a cross-section view of the sub-embodiment of the container system 300 after removal of the needle 312 and is analogous to the view of the embodiment shown in FIG.3C. The sub-embodiment of the container system 300 can include the aspects, features, relationships, etc., described previously in reference to the container system 300, and vice versa. The container system 300 can include a plunger rod 326 with a connector 328. The plug 318 of the sub-embodiment of the container system 300 can include a connector 318d that is complimentary to the connector 328 of the plunger rod 326. The plug 318 and the plunger rod 326 can thus be mechanically connected via the connector 318d and the connector 328.Alternatively, the plug 318 and the plunger rod 326 can a unitary structure. The mechanical connection or unitary aspects can facilitate placement of the plug 318 in the recess 310.

[0101] FIG. 3F is a cross-section view of the sub-embodiment of the container system 300 with the plug 318 within the recess 310 to reinforce or seal the plunger 308.

[0102] FIG. 4 shows aspects of a process 400 of aseptic fill / finish using any of the container systems (e.g., the container system 100, the container system 200, the container system 300, any sub-embodiments, etc.). The process 400 can include, at step 402, seating a closure within an opening of a container and can further include, at step 404, piercing the closure with a needle to define a hole through the closure. The process 400 can further include, at step 406, filling the container with a medicament through the needle. The process 400 can include, at step 408, removing the needle from the hole. The process 400 can further include, at step 410, sealing the hole with a plug that is fixed to a recess of the closure.

[0103] FIG. 5A and FIG. 5B show a side cross-section view of a container system 500 according to a fourth embodiment of this disclosure. The container system 500 can include aspects, features, relationships, etc., of any of the container systems 100, 200, or 300 and viceversa. For example, the container system 500 can include a container 502 with an opening 504. The container 502 can be any structure that can contain medicament such as a vial, a syringe, a bottle, an ampule, among other possibilities. The container 502 can be formed of glass, plastic (e.g., cyclic olefin copolymer, cyclic olefin polymer), among other possibilities. In embodiments, the container 502 can include a flange 506 adjacent to (e.g., surrounding) the opening 504.

[0104] The container system 500 can include a closure 508, which can be received within the opening 504. The closure 508 can be structured and arranged to seal the opening 504. In embodiments, the closure 508 can be a stopper, a plunger, a cap, among other possibilities. The closure 508 can include an inner surface 508a. When the closure 508 is seated within the opening 504 to seal the opening 504, the inner surface 508a can face the interior of the container 502. Accordingly, medicament within the container 502 can be exposed to the inner surface 508a. In some embodiments, the inner surface 508a can be coated with one or more coatings or laminations to protect the medicament from potential contamination associated with the material forming the closure 508. The coatings or laminations may include fluoropolymers or non-fluorinated materials. The closure 508 can include an outer surface 508b, which can oppose the inner surface 508a and / or face away from the inner surface 508a. The closure 508 can define a hole 516 therethrough extending between the inner surface 508a and the outer surface 508b. The hole 516 can be defined through the closure 508 during manufacturing or can be formed when a needle is inserted through the closure 508 during filling of the container 502.

[0105] The container system 500 can include a plug 518 configured to cover, plug, or otherwise seal the hole 516 in the closure 508. The plug 518 can include any of the features of plugs 118, 218, 318 described elsewhere. In some aspects, the plug 518 can be a sheet or disc of material configured to be placed onto or adjacent to the closure 508. In the specific embodiment shown in FIG. 5 A and FIG. 5B, the plug 518 can be a disc placed onto the outer surface 508b. The plug 518 can be placed onto the closure 508 after the container 502 has been filled. After being placed onto the outer surface 508b, the plug 518 effectively closes access to the hole 516 extending through the closure 508 such that significant amounts of liquids and gases cannot move into or out of the container 502 through the hole 516.

[0106] FIG. 5C through FIG. 5E show aspects of a sub-embodiment of the fourth embodiment of the container system 500. In some aspects, such as shown in embodiments depicted in FIG.5C and FIG. 5D, the plug 518 can include a protrusion 519 extending therefrom. The protrusion202400090-WQ 519 can be sized, shaped, or otherwise dimensioned to enter the hole 516 in the closure 508 when the plug 518 is placed onto the outer surface 508b. The protrusion 519 can be comprised of the same material as the plug 518 or, alternatively, another material. In some aspects, the protrusion 519 can include a deformable material (e.g., an elastomer) and can be dimensioned slightly larger than the opening of the hole 516, such that when the plug 518 is placed onto the closure 508 and secured (e.g., via a crimp seal, a snap-fit cap, or another mechanism described elsewhere in this application), the protrusion 519 is compressed enough that at least a portion thereof enters the hole 516 and forms a seal against the surfaces of the closure 508 that define the hole 516.

[0107] As shown in FIG. 5E, the container system 500 can include a cap 520. The cap 520 can be a crimp seal, a plastic snap-fit cap, or another cap mechanism described elsewhere in this application. In use, the plug 518 can be placed onto the closure 508 and then the cap 520 can be placed on top such that the plug 518 is pressed against the closure 508 to effectively seal the hole 516. The cap 520 applies pressure to the closure 508 against the container 502 and can also serve to maintain a seal between the closure 508 and the container 502. In some aspects, the plug 518 can be integrated into the cap 520 such the plug 518 is placed onto the closure 508 when the cap 520 is attached to the rest of the container system 500.

[0108] It will be appreciated that the foregoing description provides examples of the invention. However, it is contemplated that other implementations of the invention may differ in detail from the foregoing examples. All references to the invention or examples thereof are intended to reference the particular example being discussed at that point and are not intended to imply any limitation as to the scope of the invention more generally. All language of distinction and disparagement with respect to certain features is intended to indicate a lack of preference for those features, but not to exclude such from the scope of the invention entirely unless otherwise indicated.

Claims

202400090-WQ CLAIMSWhat is claimed is:

1. A closure system for containing a medicament, the closure system comprising:a container that is configured to contain the medicament;a closure that is configured to seal an opening of the container, the closure defining a hole extending therethrough; anda plug configured to contact the closure such that the plug covers the hole and blocks movement of liquid and gas into and out of the container through the hole.

2. The closure system of claim 1, wherein the closure is made of an elastomer and the plug is made of an elastomer.

3. The closure system of claim 1 or claim 2, wherein the closure includes a coating on a surface configured to be contacted by the plug.

4. The closure system of any one of the preceding claims, wherein at least one surface of the plug and at least one surface of the closure are surface treated.

5. The closure system of any one of the preceding claims, further comprising a cap that holds the closure on the container.

6. The closure system of claim 5, wherein the plug is integrated into the cap and is configured to contact the closure when the cap is placed onto the container.

7. The closure system of claim 5 or claim 6, wherein the container is a vial that includes a flange, and the cap is configured to contact the flange when the cap is placed onto the vial, such that the cap is securely attached to the vial and the plug contacts the closure.

8. A closure system for containing a medicament, the closure system comprising:a container that is configured to contain the medicament;a closure that is configured to seal an opening of the container, the closure defining a recess; anda plug that is complimentary to the recess, wherein the plug is configured to be fixed within the recess to seal or reinforce the closure.202400090-WQ 9. The closure system of claim 8, wherein the closure is made of an elastomer and the plug is made of an elastomer.

10. The closure system of claim 8 or claim 9, wherein at least one surface of the plug and at least one surface of the closure are surface treated.

11. The closure system of any one of claims 8-10, wherein:the closure defines a hole extending therethrough, andthe plug is irremovably fixed to the closure within the recess to seal the hole.

12. The closure system of any one of claims 8-11, further comprising a cap that holds the closure on the container.

13. The closure system of claim 12, wherein:the plug is fixed to the cap, andthe closure system further comprises a cover that is removably attached to the cap and that covers an outer surface of the plug.

14. The closure system of claim 8, wherein the closure comprises a first portion that is made of an elastomer and a second portion that is made of a plastic.

15. The closure system of claim 14, wherein:the plug comprises a first portion that is made of an elastomer and a second portion that is made of a plastic,the first portion of the plug, when the plug is fixed within the recess, interfaces with the first portion of the closure, andthe second portion of the plug, when the plug is fixed to the closure within the recess, interfaces with the second portion of the closure.

16. The closure system of claim 15, wherein the first portion of the plug extends between an inner surface of the plug and an outer surface of the plug.

17. The closure system of claim 15, wherein:the closure defines a hole extending therethrough, andthe plug is irremovably fixed to the closure within the recess and to seal the hole.202400090-WQ 18. The closure system of claim 14, wherein the plug is configured to be removably fixed to the closure within the recess.

19. The closure system of claim 18, wherein:the closure defines a hole extending therethrough, andthe plug, when removably fixed to the closure within the recess, seals the hole.

20. The closure system of any one of claims 8—19, wherein the container is a vial.

21. The closure system of claim 8, wherein:the container is a syringe, andthe closure is a plunger configured to move within the syringe to eject the medicament from the syringe.

22. The closure system of claim 21, wherein the plunger comprises a fastener configured to hold the plug within the recess.

23. The closure system of claim 21, wherein:the closure system further comprises a plunger rod,the plunger rod comprises a connector, andthe plug comprises a connector that is configured to connect to connector of the plunger rod.

24. The closure system of any one of claims 8-23, wherein:the closure comprises:an inner surface that faces an interior of the container when the closure seals the opening of the container;an outer surface that opposes the inner surface;an intermediate surface between the inner surface and the outer surface; and a sidewall surrounding the intermediate surface, andthe recess is recessed from the outer surface towards the inner surface and is defined by the intermediate surface and the sidewall.

25. A method of aseptically filling a container system, the method comprising: seating a closure within an opening of a container;piercing the closure with a needle to define a hole through the closure;filling the container with a medicament through the needle;removing the needle from the hole; andsealing the hole with a plug that is fixed to a recess of the closure.

26. The method of claim 25, wherein sealing the hole comprises irremovably fixing the plug to the closure within the recess.

27. The method of claim 26, wherein sealing the hole comprises removably fixing the plug to the closure within the recess.

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