Plunger assembly for sealing pharmaceutical containers at low temperatures

Abstract

A plunger assembly for sealing pharmaceutical containers is disclosed herein. According to one or more embodiments described herein, the plunger assembly has a glass transition temperature T of -65°C or lower. g The assembly may include a plunger containing an elastic material and a plunger rod coupled to the plunger. A pharmaceutical container assembly and a method for storing pharmaceutical compositions are also disclosed herein.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority under § 119 of U.S. Patent Act to U.S. Provisional Application No. 63 / 469,955, filed on 31 May 2023, the contents of which this Provisional Application is relied upon and incorporated herein by reference in its entirety.

[0002] This specification generally relates to pharmaceutical containers, and more specifically to plunger assemblies for sealing pharmaceutical containers. [Background technology]

[0003] Historically, glass has been used to produce a variety of articles. Specifically, due to its airtightness, optical clarity, and superior chemical durability compared to other materials, glass is a preferred material for pharmaceutical applications, including but not limited to vials, syringes, ampoules, cartridges, bottles, and other glass articles. These pharmaceutical containers may be sealed with plungers, stoppers, or other closures to maintain the integrity of the material stored within the container. [Overview of the project]

[0004] Low storage temperatures can cause dimensional changes in sealing components (e.g., glass or plastic containers and / or plungers), which can lead to problems with seal integrity and potential contamination of materials stored in the sealing components. Therefore, there is a continuing need for pharmaceutical containers suitable for use at low temperatures, particularly plunger assemblies for sealing pharmaceutical containers at low temperatures. This disclosure covers plunger assemblies that can be used to seal pharmaceutical containers at low temperatures, and pharmaceutical container assemblies that utilize such plunger assemblies.

[0005] According to one or more embodiments, a plunger assembly for sealing a pharmaceutical container has a glass transition temperature T of -65°C or lower. gThe plunger assembly may include an elastic material that may have a certain property. The plunger assembly may also include a plunger rod coupled to the plunger.

[0006] According to an additional embodiment, the pharmaceutical container assembly may comprise a pharmaceutical container comprising a body having an outer surface and an inner surface, and a plunger that can be inserted into an opening in the body. The radial outer surface of the plunger may form an interference fit with the inner surface of the body. The plunger has a glass transition temperature T of -65°C or lower. g It may include an elastic material that has the following properties. The interference fit may form a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The seal may be maintained when the pharmaceutical container assembly is cooled to -65°C or below.

[0007] According to an additional embodiment, a method for storing a pharmaceutical composition may include providing a pharmaceutical container assembly. The pharmaceutical container assembly may comprise a body having an outer surface and an inner surface, and a plunger that can be inserted into an opening in the body. The radial outer surface of the plunger may form an interlocking fit with the inner surface of the body. The interlocking fit may form a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The plunger may comprise an elastic material having a glass transition temperature of -65°C or less. The method may also comprise adding a biological composition or pharmaceutical composition to the pharmaceutical container. The method may further comprise inserting the plunger into the pharmaceutical container and cooling the pharmaceutical container assembly and the biological composition or pharmaceutical composition disposed within the pharmaceutical container assembly to a temperature of below -65°C. The seal may be maintained when the pharmaceutical container assembly is cooled to -65°C or below.

[0008] Additional features and advantages of the embodiments described herein are described in the following detailed description and will be readily apparent to those skilled in the art from that description, or will be recognized by practicing the embodiments described herein, including the following detailed description, claims, and accompanying drawings.

[0009] It should be understood that both the above overview and the following detailed description are intended to illustrate various embodiments and provide an outline or framework for understanding the nature and characteristics of the claimed subject matter. The accompanying drawings are included to provide a further understanding of the various embodiments and are incorporated herein and constitute part of this specification. The drawings illustrate the various embodiments described herein and, together with their descriptions, help to illustrate the principles and work of the claimed subject matter. [Brief explanation of the drawing]

[0010] [Figure 1A] A schematic cross-sectional view of a plunger assembly according to one or more embodiments shown and described herein is provided. [Figure 1B] A schematic cross-sectional view of a plunger assembly according to one or more embodiments shown and described herein is provided. [Figure 2] A schematic cross-sectional view of a pharmaceutical container assembly according to one or more embodiments shown and described herein is provided. [Figure 3A] This specification illustrates the simulated contact pressure at 25°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -60°C, according to one or more embodiments shown and described herein. [Figure 3B] Figure 3A illustrates the interface between the plunger assembly and the pharmaceutical container in a simulation, where the difference in sealing pressure is annotated using the difference in shading patterns, according to one or more embodiments shown and described herein. [Figure 4]The contact area (y-axis) as a function of temperature (x-axis) for three different cooling rates for a pharmaceutical container assembly comprising a pharmaceutical container and a plunger assembly engaged with a 5% interference fit (glass transition temperature of -60°C), according to one or more embodiments shown and described herein. [Figure 5] The contact area (y-axis) as a function of temperature (x-axis) for three different cooling rates is illustrated for a pharmaceutical container assembly comprising a pharmaceutical container and a plunger assembly engaged with a 10% interference fit (glass transition temperature of -60°C) according to one or more embodiments shown and described herein. [Figure 6] The contact area (y-axis) as a function of temperature (x-axis) for five different cooling rates for a pharmaceutical container assembly comprising a pharmaceutical container and a plunger assembly engaged with a 5% interference fit (glass transition temperature of -60°C), according to one or more embodiments shown and described herein. [Figure 7A] This specification illustrates the simulated contact pressure at 25°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C, according to one or more embodiments shown and described herein. [Figure 7B] Figure 7A illustrates the interface between the plunger assembly and the pharmaceutical container in a simulation, where the difference in sealing pressure is annotated using the difference in shading patterns, according to one or more embodiments shown and described herein. [Figure 8A] This specification illustrates the simulated contact pressure at -80°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C, according to one or more embodiments shown and described herein. [Figure 8B] Figure 8A illustrates the interface between the plunger assembly and the pharmaceutical container in a simulation, where the difference in sealing pressure is annotated using the difference in shading patterns, according to one or more embodiments shown and described herein. [Figure 9A]Depicts the simulated contact pressure at -125°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C, according to one or more embodiments shown and described herein. [Figure 9B] Illustrates the interface between the plunger assembly and the pharmaceutical container in the simulation of FIG. 9A, where the difference in seal pressure is annotated using the difference in shading pattern, according to one or more embodiments shown and described herein. [Figure 10] Illustrates the contact area (y-axis) as a function of temperature (x-axis) for five different interference fits for a pharmaceutical container assembly comprising a pharmaceutical container and a plunger assembly (having a glass transition temperature of -130°C), according to one or more embodiments shown and described herein. [Figure 11A] Depicts the simulated contact pressure at 25°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C and a butyl rubber coating layer, according to one or more embodiments shown and described herein. [Figure 11B] Illustrates the interface between the plunger assembly and the pharmaceutical container in the simulation of FIG. 11A, where the difference in seal pressure is annotated using the difference in shading pattern, according to one or more embodiments shown and described herein. [Figure 12A] Depicts the simulated contact pressure at -80°C between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C and a butyl rubber coating layer, according to one or more embodiments shown and described herein. [Figure 12B] Illustrates the interface between the plunger assembly and the pharmaceutical container in the simulation of FIG. 12A, where the difference in seal pressure is annotated using the difference in shading pattern, according to one or more embodiments shown and described herein. [Figure 13A]This specification illustrates the simulated contact pressure between a pharmaceutical container and a plunger assembly having a glass transition temperature of -130°C and a butyl rubber coating layer, according to one or more embodiments shown and described herein. [Figure 13B] Figure 13A illustrates the interface between the plunger assembly and the pharmaceutical container in a simulation, where the difference in sealing pressure is annotated using the difference in shading patterns, according to one or more embodiments shown and described herein. [Modes for carrying out the invention]

[0011] Embodiments of the present application are described here, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numerals are used throughout the drawings to refer to the same or similar parts. However, the present disclosure may be embodied in different forms and should not be construed as being limited to the embodiments described herein. Rather, these embodiments are provided so as to ensure that the present disclosure is thorough and complete and fully conveys the scope of the subject matter to those skilled in the art.

[0012] Embodiments of this disclosure relate to plunger assemblies for sealing pharmaceutical containers. The plunger assemblies have a glass transition temperature T of -65°C or lower. g A plunger assembly may comprise a plunger made of an elastic material having a certain property, and a plunger rod coupled to the plunger. The plunger assembly disclosed herein may be used in a pharmaceutical container assembly. The pharmaceutical container assembly may comprise a pharmaceutical container having a body having an outer surface and an inner surface. The plunger assembly may be inserted into an opening in the body. The radial outer surface of the plunger may form an interference fit with the inner surface of the body. The interference fit may form a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The seal may be maintained when the pharmaceutical container is cooled to below -65°C.

[0013] As used herein, the term “container seal integrity” refers to the maintenance of a seal at the interface between the pharmaceutical container and the seal assembly (e.g., between the sealing surface of the pharmaceutical container and the plunger) without gaps exceeding a threshold size, in order to maintain the probability of contaminant ingress or reduce the possibility of gas permeability below a predetermined threshold, based on the material stored in the pharmaceutical container. For example, in embodiments, USP <1207> The helium leak rate during the helium leak test described in (2016) is 1.4 × 10⁻⁶. -6 cm 3 If maintained at or below / s, container closure integrity is maintained.

[0014] As used herein, the term "CTE" refers to the coefficient of linear thermal expansion of a material at a temperature of 25°C, unless otherwise specified.

[0015] As used herein, the term "elastic material" refers to a material that has the ability to return to its original shape after being deformed by compression or other means.

[0016] As used herein, the term “biocompatible polymer” means a polymer that does not react with or adversely affect a pharmaceutical or biological composition upon contact with it.

[0017] As used herein, the term “interference fit” refers to a form of fastening between two parts that, after the parts are pressed together, create a joint that is held together by friction.

[0018] As used herein, the term “tight fit percentage” refers to the percentage difference between the radial outer diameter of the plunger and the inner diameter of the body of the pharmaceutical container.

[0019] Pharmaceutical containers, such as syringes, are typically sealed via plungers or other closures to maintain the integrity of the contained material. These closures, such as plungers, are typically made of synthetic rubber and other elastomers. The closure may be held in place by a tight fit between the closure and the pharmaceutical container. Some biomaterials (e.g., blood, serum, proteins, stem cells, and other perishable biological fluids) require storage at low temperatures, such as below -45°C, below -80°C, or even below approximately -180°C. For example, certain RNA-based vaccines may require storage at dry ice temperatures (e.g., approximately -80°C) or liquid nitrogen temperatures (e.g., approximately -180°C) to maintain their activity.

[0020] The plunger assemblies, pharmaceutical container assemblies, and methods for storing pharmaceutical compositions of this disclosure may be used at temperatures below the temperatures of conventional plungers or container assemblies, such as below -65°C. Typically, plunger assemblies used at low temperatures may not adequately seal pharmaceutical containers because the glass transition temperature of the materials used to form conventional plungers may exceed the temperature at which the pharmaceutical containers are stored. While not bound by any particular theory, it is thought that the loss of seal integrity at temperatures below -65°C may be caused by differences in thermal contraction between the various components, loss of elasticity of the plunger at temperatures below the glass transition temperature of the material from which the plunger is made, or a combination thereof.

[0021] The plunger assemblies, pharmaceutical container assemblies, and methods for storing pharmaceutical compositions of this disclosure may enable the use of lower storage temperatures, such as below -65°C, which may be required to store certain pharmaceutical and / or biological compositions.

[0022] Referring here to Figure 1A, one embodiment of a plunger assembly 100 for sealing a pharmaceutical container is schematically depicted. The plunger assembly 100 may comprise a plunger 110 and a plunger rod 120 coupled to the plunger. The plunger 110 may have an axial inner surface 112 and an axial outer surface 114. In the embodiment, the plunger rod 120 may be coupled to the axial outer surface 114, and the axial inner surface 112 may face inward towards the pharmaceutical container when the plunger assembly is inserted into the pharmaceutical container. The plunger 110 may also have a radial outer surface 113 facing radially outward.

[0023] In this embodiment, the plunger has a glass transition temperature T of -65°C or lower. g It may include an elastic material. g Below a certain temperature, the elastic material behaves as a solid (e.g., loss of elasticity), which can lead to a decrease in sealing force. In other words, when the elastic material is cooled below its glass transition temperature, it effectively behaves as two different materials: the elastic material above its transition temperature and solid glass below its transition temperature. In embodiments, the elastic material is cooled below -70°C, -80°C, -90°C, -100°C, -110°C, or even below -120°C. gIt may have. In an embodiment, the elastic material is from -65°C to -150°C, for example, from -65°C to -140°C, from -65°C to -130°C, from -65°C to -120°C, from -65°C to -110°C, from -65°C to -100°C, from -65°C to -90°C, from -65°C to -80°C, from -65°C to -70°C, from -70°C to -150°C, from -70°C to -140°C, from -70°C to -130°C, from -70°C to -120°C, from -70°C to -110°C, from -70°C to -100°C, from -70°C to -90°C, from -70°C to -80°C, from -80°C to -150°C, from -80°C to -140°C, from -80°C to -130°C, from -80°C to -120°C, from -80°C to -110°C, from -80°C to -100°C, from -80°C to -90°C, from -90°C to -150°C, from -90°C to -140°C, from -90°C to -130°C, from -90°C to -120°C, from -90°C to -110°C, from -90°C to -100°C, from -100°C to -150°C, from -100°C to -140°C, from -100°C to -130°C, from -100°C to -120, from -110°C to -150°C, from -110°C to -140°C, from -110°C to -130°C, from -110°C to -120°C, from -120°C to -150°C, from -120°C to -140°C, from -120°C to -130°C, from -130°C to -150°C, from -130° to -140°C, from -140°C to -150°C, or any combination of one or more of these ranges of T g It may have. In an embodiment, the elastic material has a glass transition temperature T of -65°C or lower g It may include a silicone rubber having

[0024] Without being bound by theory, if the glass transition temperature of the elastic material is less than the intended use temperature, the elastic material may lose its elasticity, and the loss of elasticity may cause the loss of the integrity of the seal. The maintenance of the seal of the plunger assembly can be determined by the compression of the plunger and the elasticity of the plunger at a temperature above the glass transition temperature of the plunger. Therefore, the plunger assembly disclosed herein can be used at a temperature lower than that of a conventional plunger assembly that may utilize an elastic material such as butyl rubber having a glass transition temperature above -65°C.

[0025] Pharmaceutical and biological compositions that may be stored in pharmaceutical containers may be sensitive to or react with the elastic material used in the plunger assembly. This can result in contamination of the compositions stored in the pharmaceutical container. Referring again to Figure 1, in the embodiment, the plunger assembly 100 may further include a biocompatible polymer. The biocompatible polymer can reduce or prevent the interaction between the pharmaceutical composition and the elastic material, and reduce or prevent contamination of the pharmaceutical composition resulting from the interaction. In the embodiment, the biocompatible polymer may include one or more of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkanes, copolymers thereof, and blends thereof. In the embodiment, the biocompatible polymer may include a polymer selected from the group consisting of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkanes, copolymers thereof, and combinations thereof.

[0026] In embodiments, a biocompatible polymer can form a coating layer 130 on the axial inner surface 112 of the plunger 110. In embodiments, the coating layer 130 may have a thickness of at least 3 microns, for example, at least 5 microns, at least 10 microns, at least 20 microns, at least 30 microns, at least 40 microns, or even at least 50 microns. In this embodiment, the coating layer 130 is approximately 3 microns to approximately 200 microns, for example, approximately 3 microns to approximately 175 microns, approximately 3 microns to approximately 150 microns, approximately 3 microns to approximately 125 microns, approximately 3 microns to approximately 100 microns, approximately 3 microns to approximately 75 microns, approximately 3 microns to approximately 50 microns, approximately 3 microns to approximately 25 microns, approximately 25 microns to approximately 200 microns, approximately 25 microns to approximately 175 microns, approximately 25 microns to approximately 150 microns, approximately 25 microns to approximately 125 microns, approximately 25 microns to approximately 100 microns, approximately 25 microns to approximately 75 microns, approximately 25 microns to approximately 50 microns, approximately 50 microns to approximately 200 microns, approximately 50 microns to approximately 175 microns, approximately 50 microns to approximately 125 microns. The thickness may be approximately 50 microns to 100 microns, approximately 50 microns to 75 microns, approximately 75 microns to 200 microns, approximately 75 microns to 175 microns, approximately 75 microns to 125 microns, approximately 75 microns to 100 microns, approximately 100 microns to 200 microns, approximately 100 microns to 175 microns, approximately 100 microns to 150 microns, approximately 100 microns to 125 microns, approximately 125 microns to 200 microns, approximately 125 microns to 175 microns, approximately 125 microns to 150 microns, approximately 150 microns to 200 microns, approximately 150 microns to 175 microns, approximately 175 microns to 200 microns, or any combination of one or more of these ranges.

[0027] In one embodiment, the coating layer 130 is more than 0% to 75% of the total thickness of the plunger 110, for example, about 0% to about 70%, about 0% to about 60%, about 0% to about 50%, about 0% to about 40%, about 0% to about 30%, about 0% to about 20%, about 0% to about 10%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 75%, about 20% to about 70%, about 20% to about 60%, about 20% The thickness may be approximately 50%, 20% to 40%, 20% to 30%, 30% to 75%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 75%, 40% to 60%, 40% to 50%, 50% to 75%, 50% to 70%, 50% to 60%, 60% to 70%, 70% to 75%, or any combination of one or more of these ranges.

[0028] The coating layer 130 may be formed on the axial inner surface 112 of the plunger 110 by thermoforming, spray coating, dip coating, or other coating processes. In embodiments, the coating layer 130 may be thermoformed onto the plunger 110. In embodiments, the coating layer 130 may be spray coated onto the plunger 110 and then cured. In embodiments, the coating layer 130 may be photocured after being spray coated onto the plunger 110. In embodiments, the coating layer 130 may contain a biocompatible polymer that is curable upon exposure to UV light, and photocuring may involve exposing the biocompatible polymer to UV light for a period of time sufficient to cure the polymer.

[0029] In embodiments, the biocompatible polymer may be scattered within the elastic material. In embodiments, the biocompatible polymer may be scattered within the elastic material throughout the entire plunger 110. In embodiments, the biocompatible polymer may be scattered within the elastic material through only a portion of the plunger 110. As shown in Figure 1B, in embodiments, the biocompatible polymer may be scattered within the elastic material on the axial inner surface 112 of the plunger 110, forming a scattered polymer layer 140. In embodiments, the scattered polymer layer 140 may have a thickness of at least 3 microns, for example, at least 5 microns, at least 10 microns, at least 20 microns, at least 30 microns, at least 40 microns, or even at least 50 microns. In this embodiment, the scattered polymer layers 140 are approximately 3 microns to approximately 200 microns, for example, approximately 3 microns to approximately 175 microns, approximately 3 microns to approximately 150 microns, approximately 3 microns to approximately 125 microns, approximately 3 microns to approximately 100 microns, approximately 3 microns to approximately 75 microns, approximately 3 microns to approximately 50 microns, approximately 3 microns to approximately 25 microns, approximately 25 microns to approximately 200 microns, approximately 25 microns to approximately 175 microns, approximately 25 microns to approximately 150 microns, approximately 25 microns to approximately 125 microns, approximately 25 microns to approximately 100 microns, approximately 25 microns to approximately 75 microns, approximately 25 microns to approximately 50 microns, approximately 50 microns to approximately 200 microns, approximately 50 microns to approximately 175 microns, and approximately 50 microns to approximately 125 microns. The thickness may be approximately 50 microns to 100 microns, approximately 50 microns to 75 microns, approximately 75 microns to 200 microns, approximately 75 microns to 175 microns, approximately 75 microns to 125 microns, approximately 75 microns to 100 microns, approximately 100 microns to 200 microns, approximately 100 microns to 175 microns, approximately 100 microns to 150 microns, approximately 100 microns to 125 microns, approximately 125 microns to 200 microns, approximately 125 microns to 175 microns, approximately 125 microns to 150 microns, approximately 150 microns to 200 microns, approximately 150 microns to 175 microns, approximately 175 microns to 200 microns, or any combination of one or more of these ranges.

[0030] In this embodiment, the scattered polymer layers 140 comprise more than 0% to 75% of the total thickness of the plunger 110, for example, about 0% to about 70%, about 0% to about 60%, about 0% to about 50%, about 0% to about 40%, about 0% to about 30%, about 0% to about 20%, about 0% to about 10%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 75%, about 20% to about 70%, about 20% to about 60%, about 2 The thickness may be 0% to approximately 50%, approximately 20% to approximately 40%, approximately 20% to approximately 30%, approximately 30% to approximately 75%, approximately 30% to approximately 70%, approximately 30% to approximately 60%, approximately 30% to approximately 50%, approximately 30% to approximately 40%, approximately 40% to approximately 75%, approximately 40% to approximately 70%, approximately 40% to approximately 60%, approximately 40% to approximately 50%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 50% to approximately 60%, approximately 60% to approximately 75%, approximately 60% to approximately 70%, approximately 70% to approximately 75%, or any combination of one or more of these ranges.

[0031] In this embodiment, the scattered polymer layers 140 are based on the total weight of the scattered polymer layers 140 and are in amounts greater than 0% to 100% by weight, for example, greater than 0% to 90% by weight, greater than 0% to 80% by weight, greater than 0% to 70% by weight, greater than 0% to 60% by weight, greater than 0% to 50% by weight, greater than 0% to 40% by weight, greater than 0% to 30% by weight, greater than 0% to 20% by weight, greater than 0% to 10% by weight, greater than 10% to 100% by weight, greater than 10% to 90% by weight, greater than 10% by weight ~80wt%, over 10wt%~70wt%, over 10wt%~60wt%, over 10wt%~50wt%, over 10wt%~40wt%, over 10wt%~30wt%, over 10wt%~20wt%, over 20wt%~100wt%, 2 More than 0% to 90% by weight, More than 20% to 80% by weight, More than 20% to 70% by weight, More than 20% to 60% by weight, More than 20% to 50% by weight, More than 20% to 40% by weight, More than 20% to 30% by weight, More than 30% to 100% by weight Amount %, more than 30 wt% to 90 wt%, more than 30 wt% to 80 wt%, more than 30 wt% to 70 wt%, more than 30 wt% to 60 wt%, more than 30 wt% to 50 wt%, more than 30 wt% to 40 wt%, more than 40 wt% to 100 wt%, 40 wt% More than 90% by weight, more than 40% by weight ~ 80% by weight, more than 40% by weight ~ 70% by weight, more than 40% by weight ~ 60% by weight, more than 40% by weight ~ 50% by weight, more than 50% by weight ~ 100% by weight, more than 50% by weight ~ 90% by weight, more than 50% by weight ~ 80% by weight, 5 The biocompatible polymer may contain a concentration of over 0% to 70% by weight, over 50% to 60% by weight, over 60% to 100% by weight, over 60% to 90% by weight, over 60% to 80% by weight, over 60% to 70% by weight, over 70% to 100% by weight, over 70% to 90% by weight, over 70% to 80% by weight, over 80% to 100% by weight, over 80% to 90% by weight, over 90% to 100% by weight, or any combination of one or more of these ranges.

[0032] Referring here to Figure 2, in an embodiment, the plunger assembly 100 may be used in a pharmaceutical container assembly 200. The pharmaceutical container assembly 200 may comprise a pharmaceutical container 202 and the plunger assembly 100. The pharmaceutical container 202 may comprise a body 210 having an inner surface 212 and an outer surface 214. In an embodiment, the pharmaceutical container 202 may be a syringe. Although the pharmaceutical container assembly 200 is depicted as a syringe in Figure 2, it should be understood that the pharmaceutical container 202 may have other form factors, including but not limited to Vacutainers®, cartridges, vials, bottles, flasks, bottles, tubes, beakers, etc. The plunger assembly 100 may be inserted into an opening in the body 210. The plunger assembly 100 may have a radial outer surface 113 of the plunger 110, which is the surface of the plunger 110 that contacts the inner surface 212 of the body 210. The radial outer surface 113 of the plunger 110 can form an interlocking fit with the inner surface 212 of the body 210. In an embodiment, the interlocking fit can form a seal between the inner surface 212 of the body 210 and the radial outer surface 113 of the plunger 110. In an embodiment, the seal can be maintained when the pharmaceutical container assembly 200 is cooled to a temperature of -65°C or lower.

[0033] In one embodiment, the interference fit of the pharmaceutical container assembly 200 may be at least 2%, for example, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or even more than 10%. In one embodiment, the interference fit of the pharmaceutical container assembly 200 may be about 2% to about 10%, for example, about 2% to about 9%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 2% to about 5%, about 2% to about 4%, about 2% to about 4%, about 2% to about 3%, about 3% to about 10%, about 3% to about 9%, about 3% to about 8%, about 3% to about 7%, about 3% to about 6%, about 3% to about 5%, about 3% to about 4%, about 4% to about 10%, about 4% to about 9%, about 4% to about 8%. , approximately 4% to 7%, approximately 4% to 6%, approximately 4% to 5%, approximately 5% to 10%, approximately 5% to 9%, approximately 5% to 8%, approximately 5% to 7%, approximately 5% to 6%, approximately 6% to 10%, approximately 6% to 9%, approximately 6% to 8%, approximately 6% to 7%, approximately 7% to 10%, approximately 7% to 9%, approximately 7% to 8%, approximately 8% to 10%, approximately 8% to 9%, approximately 9% to 10%, or any combination of one or more of these ranges. Although not bound by theory, it is thought that interference fits of less than 2% may not provide sufficient container closure integrity, even if the glass transition temperature of the elastic material is below the temperature at which the pharmaceutical container assembly is stored. If the difference between the CTE of the elastic material and the CTE of the pharmaceutical container assembly body is sufficiently large, it is thought that the seal may be adversely affected regardless of the glass transition temperature of the elastic material.

[0034] In embodiments, the seal can be maintained when the pharmaceutical container assembly 200 is cooled to a temperature of -65°C or below, -70°C or below, -80°C or below, -90°C or below, -100°C or below, -110°C or below, or even below -120°C. In embodiments, the seal can be maintained when the pharmaceutical container assembly 200 is cooled to a temperature of -65°C to -150°C, for example, -65°C to -140°C, -65°C to -130°C, -65°C to -120°C, -65°C to -110°C, -65°C to -100°C, -65°C to -90°C, -65°C to -80°C, -65°C to -70°C, -70°C to -150°C, or -70°C to -1 40℃, -70℃~-130℃, -70℃~-120℃, -70℃~-110℃, -70℃~-100℃, -70℃~-90℃, -70℃~-80℃, -80℃~-150℃, -80℃~-140℃, -80℃~-130℃, -80℃~-120℃, -80℃~-110℃, -80℃~-100℃, -80℃~-90℃, - 90℃~-150℃, -90℃~-140℃, -90℃~-130℃, -90℃~-120℃, -90℃~-110℃, -90℃~-100℃, -100℃~-150℃, -100℃~-140℃, -100℃~-130℃, -100℃~-120℃, -100℃~-110℃, -110℃~-150℃, -110℃~-1 The seal can be maintained when cooled to temperatures of 40°C, -110°C to -130°C, -110°C to -120°C, -120°C to -150°C, -120°C to -140°C, -120°C to -130°C, -130°C to -150°C, -130°C to -140°C, -140°C to -150°C, or any combination of one or more of these ranges. Although not bound by theory, since the glass transition temperature of the elastic material of the plunger is below -65°C, and therefore the elasticity of the elastic material can be maintained while cooling, it is considered that the compression of the elastic material of the plunger 110 of the plunger assembly 100 by the inner surface 212 of the body 210 is maintained while cooling, and the seal can be maintained at temperatures below -65°C.

[0035] In embodiments, the helium leak rate of a sealed container is, by reference, incorporated in whole herein by reference, USP <1207> During the helium leak test described in (2016), 1.4 × 10 -6 cm 3It may be less than / s. 1.4 × 10 -6 cm 3 A helium leak rate of less than / s indicates the maintenance of a seal at the interface between the pharmaceutical container and the plunger assembly, with no gaps exceeding a threshold size, to maintain the probability of contaminant ingress below a predetermined threshold based on the material stored in the pharmaceutical container, or to reduce the possibility of gas permeability.

[0036] In embodiments, the body 210 of the pharmaceutical container 202 may include glass or polymer glass. In embodiments, the glass may be an aluminosilicate glass composition. In embodiments, the glass may be a glass composition such as that disclosed in U.S. Patent No. 8,551,898, which is incorporated herein by reference in whole, sold by Corning® Corporation as Valor® glass, and disclosed in U.S. Patent No. 9,145,329, which is incorporated herein by whole, <660> The glass may be an aluminosilicate glass composition that meets the criteria of Type 1 as defined in [reference]. In embodiments, the glass may be an aluminosilicate glass such as that disclosed in U.S. Patent No. 10,640,415, filed November 29, 2017, entitled Lithium Containing Aluminosilicate Glasses, which is incorporated in whole by reference, or that disclosed in U.S. Patent Publication No. 2020 / 0290920, filed September 17, 2020, entitled Chemically Durable Aluminosilicate Glass Compositions and Glass Articles Formed Therefrom, which is incorporated in whole by reference. In embodiments, the glass may be an aluminosilicate glass composition that has undergone an etching process such as acid etching or fluoride etching to remove deposits on the inner surface 212 of the pharmaceutical container assembly 200. In the embodiment, the glass may be 33-expanded borosilicate glass, such as that sold by DWK Life Sciences as KIMBAL® 33 or by Schott as BOROFLOAT® 33. Expanded 33 glass has a thermal expansion coefficient of 33 and is USP <660> This is a type 1A glass. In embodiments, the glass may be 51 expanded borosilicate glass, such as that sold by DWK Life Sciences as KIMBAL® 51, or by Corning® as 51-D clear borosilicate glass tube. Expanded 51 glass has a thermal expansion coefficient of 51 and is USP <660> This is a type 1B glass.In embodiments where the glass is 33-expanded glass or 51-expanded borosilicate glass, the outer surface 214 of the pharmaceutical container 202 may be coated with an external coating, for example, a suitable container may be a coated container sold by Corning® under the trademark Velocity®.

[0037] In embodiments, the glass may be reinforced aluminosilicate glass. In embodiments, reinforced aluminosilicate glass may be formed by ion exchange of aluminosilicate glass in a molten salt bath. The ion exchange process may be carried out in an ion exchange medium under processing conditions such as those disclosed in U.S. Patent No. 8,551,898, which is incorporated herein by reference in whole, and those disclosed in U.S. Patent No. 9,145,329, which is incorporated herein by reference in whole. However, the ion exchange process is not particularly limited, and it should be understood that other processes are contemplated herein.

[0038] Referring again to Figure 2, in an embodiment, a method for storing a pharmaceutical composition may include providing a pharmaceutical container assembly 200. The pharmaceutical container assembly 200 may comprise a pharmaceutical container 202 and a plunger assembly 100. The pharmaceutical container 202 may comprise a body 210 having an inner surface 212 and an outer surface 214. The plunger assembly 100 may comprise a plunger 110 that can be inserted into an opening in the body 210. The plunger 110 may have a radial outer surface 113, which is the portion of the outer surface of the plunger 110 that contacts the inner surface 212 of the body 210. The radial outer surface 113 may form an interlocking fit with the inner surface 212. In an embodiment, the interlocking fit may form a seal between the inner surface 212 and the axial outer surface 114. The method may further include adding a biological composition or pharmaceutical composition to the pharmaceutical container. The method may include inserting a plunger 110 into a pharmaceutical container 202 and cooling the pharmaceutical container assembly 200 and the biological or pharmaceutical composition contained within the pharmaceutical container assembly 200 to a temperature below -65°C. The seal may be maintained when the pharmaceutical container assembly 200 is cooled to a storage temperature of -65°C or below. In embodiments, the biological or pharmaceutical composition is added to the pharmaceutical container before the plunger is inserted into the pharmaceutical composition. In embodiments, the biological or pharmaceutical composition is added to the pharmaceutical container after the plunger has been inserted into the pharmaceutical container.

[0039] In the embodiment, the seal can be maintained at storage temperatures below -70°C, below -80°C, below -90°C, below -100°C, below -110°C, below -120°C, below -130°C, below -140°C, or even below -150°C. In the embodiment, the seal can be maintained at storage temperatures of -65°C to -150°C, for example, -65°C to -140°C, -65°C to -130°C, -65°C to -120°C, -65°C to -110°C, -65°C to -100°C, -65°C to -90°C, -65°C to -80°C, -65°C to -70°C, -70°C to -150°C, -70°C to -140°C, -70°C to -130℃, -70℃~-120℃, -70℃~-110℃, -70℃~-100℃, -70℃~-90℃, -70℃~-80℃, -80℃~-150℃, -80℃~-140℃, -80℃~-130℃, -80℃~-120℃, -80℃~-110℃, -80℃~-100℃, -80℃~-90℃, -90℃~ -150℃, -90℃~-140℃, -90℃~-130℃, -90℃~-120℃, -90℃~-110℃, -90℃~-100℃, -100℃~-150℃, -100℃~-140℃, -100℃~-130℃, -100℃~-120℃, -100℃~-110℃, -110℃~-150℃, -110℃~- It should be maintained at storage temperatures of 140°C, -110°C to -130°C, -110°C to -120°C, -120°C to -150°C, -120°C to -140°C, -120°C to -130°C, -130°C to -150°C, -130°C to -140°C, -140°C to -150°C, or any combination of one or more of these ranges.

[0040] In the embodiment, the cooling of the pharmaceutical container assembly 200 may be carried out at a rate of -1°C / min or more, for example, -3°C / min or more, -5°C / min or more, -10°C / min or more, -20°C / min or more, -30°C / min or more, -40°C / min or more, -50°C / min or more, -60°C / min or more, -70°C / min or more, -80°C / min or more, -90°C / min or more, or even -100°C / min or more. In this configuration, the cooling of the pharmaceutical container assembly 200 is performed at a rate of -1°C / min to -100°C / min, for example, -1°C / min to -90°C / min, -1°C / min to -80°C / min, -1°C / min to -70°C / min, -1°C / min to -60°C / min, -1°C / min to -50°C / min, -1°C / min to -40°C / min, -1°C / min to -30°C / min, -1°C / min to -20°C / min, -1°C / min to -10°C / min, -1°C / min to -5°C / min, -1°C / min to -3°C / min, -3°C / min to -100°C / min, and -3°C / min to -90°C / min. -3℃ / min to -80℃ / min, -3℃ / min to -70℃ / min, -3℃ / min to -60℃ / min, -3℃ / min to -50℃ / min, -3℃ / min to -40℃ / min, -3℃ / min to -30℃ / min, -3℃ / min to -20℃ / min, -3℃ / min to -10℃ / min, -3℃ / min to -5℃ / min, -5℃ / min to -100℃ / min, -5℃ / min to -90℃ / min, -5℃ / min to -80℃ / min, -5℃ / min to -70℃ / min, -5℃ / min to -60℃ / min, -5℃ / min to -50℃ / min, -5℃ / min to -40℃ / min, - 5℃ / min to -30℃ / min, -5℃ / min to -20℃ / min, -5℃ / min to -10℃ / min, -10℃ / min to -100℃ / min, -10℃ / min to -90℃ / min, -10℃ / min to -80℃ / min, -10℃ / min to -70℃ / min, -10℃ / min to -60℃ / min, -10℃ / min to -50℃ / min, -10℃ / min to -40℃ / min, -10℃ / min to -30℃ / min, -10℃ / min to -20℃ / min, -20℃ / min to -100℃ / min, -20℃ / min to -90℃ / min, -20℃ / min to -80℃ / min, -2 0℃ / min to -70℃ / min, -20℃ / min to -60℃ / min, -20℃ / min to -50℃ / min, -20℃ / min to -40℃ / min, -20℃ / min to -30℃ / min, -30℃ / min to -100℃ / min, -30℃ / min to -90℃ / min, -30℃ / min to -80℃ / min, -30℃ / min to -70℃ / min, -30℃ / min to -60℃ / min, -30℃ / min to -50℃ / min, -30℃ / min to -40℃ / min, -40℃ / min to -100℃ / min, -40℃ / min to -90℃ / min, -40℃ / min to -80℃ / min,-40℃ / min to -70℃ / min, -40℃ / min to -60℃ / min, -40℃ / min to -50℃ / min, -50℃ / min to -100℃ / min, -50℃ / min to -90℃ / min, -50℃ / min to -80℃ / min, -50℃ / min to -70℃ / min, -50℃ / min to -60℃ / min, -60℃ / min to -100℃ / min, -60℃ / min to -90℃ / min, -60 The process can be carried out at speeds of -°C / min to -80°C / min, -60°C / min to -70°C / min, -70°C / min to -100°C / min, -70°C / min to -90°C / min, -70°C / min to -80°C / min, -80°C / min to -100°C / min, -80°C / min to -90°C / min, -90°C / min to -100°C / min, or a combination of one or more of these ranges. [Examples]

[0041] The embodiments of this application are further clarified by the following examples. It should be understood that these examples are not intended to limit the embodiments described above.

[0042] For the simulated contact pressure tests in the following examples, the finite element analysis (FEA) software Abaqus was used for simulations in all examples. An axisymmetric model was used for the model. An elastic material model was used for the glass container, and a viscoelastic material model was used for the plunger's rubber stopper. A surface contact model was used between the stopper and the glass container. The interference fit strain can be determined by the interference contact. This model takes into account the temperature change of the CTE. The temperature of the entire system decreases from room temperature of 25°C to -130°C. Then, the contact area between the glass container and the stopper can be measured using post-processing of the Abaqus software.

[0043] Comparative Example 1 - Effect of Cooling Rate and Tight Fit on Container Closure Integrity In Comparative Example 1, T at -60°C g The effects of cooling rate and tight fit on container closure integrity of pharmaceutical container assemblies having a plunger assembly are being investigated. The plunger in Comparative Example 1 contains butyl rubber.

[0044] As shown in Figures 3A and 3B, the butyl rubber plunger exhibits good contact pressure at a temperature of 25°C. In Figures 4 and 5, the tight fit between the plunger assembly and the pharmaceutical container was adjusted to 5% to 10%, respectively, and the container assembly was cooled at three different cooling rates to determine the effect of the cooling rate and tight fit percentage on container closure integrity. The butyl rubber plunger was found to be suitable for use at approximately -60°C. g As shown in Figures 4 and 5, an increase in the interference fit from 5% in Figure 4 to 10% in Figure 5 did not affect the plunger failure temperature. Figures 4 and 5 also show little effect on the failure rate by varying the cooling rate between -1°C / min, -2°C / min, and -3°C / min. Figures 4 and 5 illustrate that the primary cause of failure is the plunger's glass transition temperature. In Figure 6, the effect of the cooling rate on container seal integrity was further investigated at faster cooling rates. In the simulation shown in Figure 6, the simulated interference fit was 5%, and the glass transition temperature of the plunger material was -60°C. Figure 6 shows that even more extreme cooling rates, such as -30°C / min, -50°C / min, and -100°C / min, have only a slight effect on the failure rate of the container seal, again illustrating that the primary driving force of failure is the plunger's glass transition temperature.

[0045] Example 2 - Effect of glass transition temperature on container closure integrity In Example 2, the effect of glass transition temperature on container closure integrity was investigated by simulating a pharmaceutical container assembly containing a silicone rubber plunger with a glass transition temperature of approximately -130°C. This simulation was performed at 25°C, -80°C, and -125°C to determine container closure integrity at low temperatures.

[0046] As shown in Figures 7A and 7B, the reduced glass transition temperature of the plunger did not adversely affect the plunger's performance at 25°C. The simulated contact pressure shown in Figures 7A and 7B, and furthermore, Figures 8A and 8B illustrate that at -80°C, the plunger still maintains sufficient contact pressure to maintain container closure integrity, and that reducing the plunger's glass transition temperature from -60°C to -130°C reduced the failure temperature of the pharmaceutical container assembly. Figures 9A and 9B show that container closure integrity was still maintained at a temperature of -125°C.

[0047] Example 3 - Effect of tight fit on container closure integrity In Example 3, the effect of the tight fit on container closure integrity was investigated by simulating pharmaceutical container assemblies containing silicone rubber plungers with a glass transition temperature of approximately -130°C at tight fit percentages of 1%, 2%, 3%, 5%, and 10%.

[0048] As shown in Figure 10, at lower interference fit percentages, such as 1%, the interference fit increased the failure temperature to well above the plunger's glass transition temperature. Higher interference fit percentages reduced the failure temperature, but the effect of the interference fit percentage on container closure integrity was most pronounced at lower fit percentages and decreased as the interference fit percentage increased. Figure 10 shows that there is a minimum interference fit percentage that compensates for the shrinkage deformation caused by the CTE mismatch between the plunger and the pharmaceutical container, but increases above this minimum do not affect container closure integrity as significantly as the plunger's glass transition temperature.

[0049] Example 4 - Effect of biocompatible polymer coating on container closure integrity In Example 4, the effect of a biocompatible polymer coating on container closure integrity was investigated by simulating a 200-micron thick butyl rubber coating on the inner surface of a silicone rubber plunger having a glass transition temperature of -130°C.

[0050] Figures 11A and 11B show the simulated contact pressure at 25°C. Figures 12A and 12B show the simulated contact pressure at -80°C. Figures 13A and 13B show the simulated contact pressure at -130°C. In summary, Figures 11A to 13B show that adding a butyl rubber coating to the plunger did not hinder the maintenance of container closure integrity at temperatures as low as -130°C, even though this coating has a higher glass transition temperature (approximately -60°C) than the silicone rubber plunger. The seal was maintained at temperatures similar to those simulated in Example 2, which did not have a biocompatible polymer coating.

[0051] According to a first aspect of this disclosure, a plunger assembly for sealing a pharmaceutical container has a glass transition temperature T of -65°C or lower. g The plunger assembly may include a plunger made of an elastic material that may have a certain property. The plunger assembly may also include a plunger rod coupled to the plunger.

[0052] A second aspect of the present disclosure may include a plunger assembly according to the first aspect, wherein the plunger has an inner surface and an outer surface, the plunger rod is coupled to the outer surface of the plunger, and the inner surface faces inward towards the pharmaceutical container when the plunger assembly is inserted into the pharmaceutical container.

[0053] A third aspect of this disclosure may include a plunger assembly according to the first or second aspect, further comprising a biocompatible polymer.

[0054] A fourth aspect of the present disclosure may include the plunger assembly according to the third aspect, wherein the biocompatible polymer comprises one or more of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkanes, and copolymers or blends thereof.

[0055] A fifth aspect of the present disclosure may include a plunger assembly according to the third or fourth aspect, wherein the biocompatible polymer forms a coating layer on the inner surface of the plunger.

[0056] A sixth aspect of the present disclosure may include the plunger assembly according to the fifth aspect, wherein the coating layer has a thickness of at least 3 microns.

[0057] A seventh aspect of the present disclosure may include a plunger assembly according to the fifth or sixth aspect, wherein the coating layer has a thickness of more than 0% to 75% of the total thickness of the plunger.

[0058] An eighth aspect of the present disclosure may include a plunger assembly according to the fifth or sixth aspect, wherein the coating layer has a thickness of about 25 microns to about 200 microns.

[0059] A ninth aspect of the present disclosure may include a plunger assembly according to any one of the fifth to eighth aspects, wherein the coating layer is thermoformed onto the plunger.

[0060] A tenth aspect of the present disclosure may include a plunger assembly according to any one of the fifth to eighth aspects, wherein the coating layer is spray-coated onto the plunger.

[0061] An eleventh aspect of the present disclosure may include a plunger assembly according to the tenth aspect, wherein the coating is spray-coated onto the plunger and then photocured.

[0062] A twelfth aspect of the present disclosure may include a plunger assembly according to the third or fourth aspect, wherein the biocompatible polymer is dispersed within the elastic material.

[0063] A thirteenth aspect of the present disclosure may include a plunger assembly according to the twelfth aspect, wherein the biocompatible polymer is scattered within the elastic material on the inner surface of the plunger, forming scattered polymer layers.

[0064] A fourteenth aspect of the present disclosure may include the plunger assembly according to the thirteenth aspect, wherein the scattered polymer layers comprise more than 0% to 100% by weight of the biocompatible polymer, based on the total weight of the scattered polymer layers.

[0065] A fifteenth aspect of this disclosure relates to an elastic material having a glass transition temperature T of -80°C or lower. g This may include a plunger assembly as described in any one of the prior embodiments, having the following characteristics:

[0066] A sixteenth aspect of this disclosure relates to an elastic material having a glass transition temperature T of -120°C or lower. g This may include a plunger assembly as described in any one of the prior embodiments, having the following characteristics:

[0067] A 17th aspect of this disclosure relates to an elastic material having a glass transition temperature T of -65°C or lower. g The plunger assembly may include a silicone rubber having the properties described in any one of the prior embodiments.

[0068] According to a 18th aspect of the present disclosure, a pharmaceutical container assembly may comprise a pharmaceutical container comprising a body having an outer surface and an inner surface, and a plunger that can be inserted into an opening in the body. The radial outer surface of the plunger may form an interlocking fit with the inner surface of the body. The plunger has a glass transition temperature T of -65°C or lower. gIt may include an elastic material that has the following properties. The interference fit may form a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The seal may be maintained when the pharmaceutical container assembly is cooled to -65°C or below.

[0069] A 19th aspect of this disclosure is a helium leak rate of the sealed container being 1.4 × 10⁻⁶ at a temperature of -65°C. -6 cm 3 This may include the pharmaceutical container assembly described in the 18th embodiment, which is less than or equal to / s.

[0070] A 20th aspect of the present disclosure may include a pharmaceutical container assembly according to the 18th or 19th aspect, wherein the interference fit is at least 2%, and the percentage of the interference fit is the percentage difference between the diameter of the radially outer surface of the plunger and the diameter of the inner surface of the body.

[0071] A 21st aspect of this disclosure may include a pharmaceutical container assembly according to any one of the 18th to 20th aspects, wherein the interference fit is at least 5%.

[0072] A 22nd aspect of the present disclosure may include a pharmaceutical container assembly according to any one of the 18th to 21st aspects, wherein the plunger further comprises a biocompatible polymer.

[0073] A 23rd aspect of the present disclosure may include a pharmaceutical container assembly according to the 22nd aspect, wherein the biocompatible polymer comprises one or more of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkanes, and copolymers or blends thereof.

[0074] A 24th aspect of this disclosure may include a pharmaceutical container assembly according to the 22nd or 23rd aspect, wherein the biocompatible polymer forms a coating layer on the inner surface of the plunger.

[0075] A 25th aspect of the present disclosure may include a pharmaceutical container assembly according to the 24th aspect, wherein the coating layer has a thickness of at least 3 microns.

[0076] A 26th aspect of the present disclosure may include a pharmaceutical container assembly according to the 24th or 25th aspect, wherein the coating layer has a thickness of more than 0% to 75% of the total thickness of the plunger.

[0077] A 27th aspect of the present disclosure may include a pharmaceutical container assembly according to the 24th or 25th aspect, wherein the coating layer has a thickness of about 25 microns to about 200 microns.

[0078] A 28th aspect of the present disclosure may include a pharmaceutical container assembly according to any one of the 24th to 27th aspects, wherein the coating layer is thermoformed on the plunger.

[0079] A 29th aspect of the present disclosure may include a pharmaceutical container assembly according to any one of the 24th to 27th aspects, wherein the coating layer is spray-coated onto the plunger.

[0080] A 30th aspect of the present disclosure may include a pharmaceutical container assembly according to the 29th aspect, wherein the coating is spray-coated onto the plunger and then photocured.

[0081] A 31st aspect of this disclosure may include a pharmaceutical container assembly according to the 22nd or 23rd aspect, wherein the biocompatible polymer is dispersed within the elastic material.

[0082] A 32nd aspect of the present disclosure may include a pharmaceutical container assembly according to the 31st aspect, wherein the biocompatible polymer is dispersed within the elastic material.

[0083] A 33rd aspect of the present disclosure may include a pharmaceutical container assembly according to the 32nd aspect, wherein the biocompatible polymer is scattered within the elastic material on the inner surface of the plunger, forming a scattered polymer layer.

[0084] A 34th aspect of this disclosure is a state in which the elastic material has a glass transition temperature T of -80°C or lower. g This may include a pharmaceutical container assembly according to any one of the 18th to 33rd embodiments, having the following characteristics:

[0085] A 35th aspect of this disclosure relates to an elastic material having a glass transition temperature T of -120°C or higher. g This may include a pharmaceutical container assembly according to any one of the 18th to 34th embodiments, having the following characteristics:

[0086] A 36th aspect of this disclosure relates to an elastic material having a glass transition temperature T of -65°C or lower. g This may include a pharmaceutical container assembly according to any one of the 18th to 35th embodiments, comprising silicone rubber having the property.

[0087] A 37th aspect of this disclosure may include a pharmaceutical container assembly according to any one of the 18th to 36th aspects, wherein the body of the pharmaceutical container includes polymer glass.

[0088] A 38th aspect of the present disclosure may include a pharmaceutical container assembly according to any one of the 18th to 37th aspects, wherein the seal is maintained when the container is cooled to -80°C or below.

[0089] A 39th aspect of the present disclosure may include a pharmaceutical container assembly according to any one of the 18th to 38th aspects, wherein the seal is maintained when the container is cooled to -120°C or below.

[0090] A forty-th aspect of this disclosure may include a pharmaceutical container assembly according to any one of the 18th to 30th-19th aspects, wherein the pharmaceutical container is a syringe.

[0091] A forty-first aspect of this disclosure may include a pharmaceutical container assembly according to any one of the 18th to 30th-19th aspects, wherein the pharmaceutical container is a cartridge.

[0092] According to a forty-second aspect of the present disclosure, a method for storing a pharmaceutical composition includes providing a pharmaceutical container assembly. The pharmaceutical container assembly may comprise a body having an outer surface and an inner surface, and a plunger that can be inserted into an opening in the body. The radial outer surface of the plunger may form an interlocking fit with the inner surface of the body. The interlocking fit may form a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The plunger may comprise an elastic material having a glass transition temperature of -65°C or less. The method may also comprise adding a biological composition or pharmaceutical composition to the pharmaceutical container. The method may further comprise inserting the plunger into the pharmaceutical container and cooling the pharmaceutical container assembly and the biological composition or pharmaceutical composition disposed within the pharmaceutical container assembly to a temperature of below -65°C. The seal may be maintained when the pharmaceutical container assembly is cooled to -65°C or below.

[0093] A forty-third aspect of the present disclosure may include a method for storing the pharmaceutical composition according to the forty-second aspect, wherein the biological composition or the pharmaceutical composition is added to the pharmaceutical container before the plunger is inserted into the pharmaceutical container.

[0094] A forty-fourth aspect of this disclosure may include a method for storing the pharmaceutical composition according to the forty-second aspect, wherein the biological composition or the pharmaceutical composition is added to the pharmaceutical container after the plunger has been inserted into the pharmaceutical container.

[0095] It will be apparent to those skilled in the art that various modifications and changes can be made to the embodiments described herein without departing from the spirit or scope of the claimed subject matter. Therefore, this specification is intended to encompass modifications and deviations to the various embodiments described herein, insofar as such modifications and changes fall within the scope of the appended claims and their equivalents.

Claims

1. A plunger assembly for sealing a pharmaceutical container, wherein the plunger assembly is Glass transition temperature T below -65°C ｇ A plunger comprising an elastic material having, A plunger assembly comprising a plunger rod coupled to the plunger.

2. The plunger assembly according to claim 1, wherein the plunger has an inner surface and an outer surface, the plunger rod is coupled to the outer surface of the plunger, and the inner surface faces inward towards the pharmaceutical container when the plunger assembly is inserted into the pharmaceutical container.

3. The plunger assembly according to claim 1 or 2, further comprising a biocompatible polymer.

4. The plunger assembly according to claim 3, wherein the biocompatible polymer comprises one or more of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkane, and copolymers or blends thereof.

5. The plunger assembly according to claim 3 or 4, wherein the biocompatible polymer forms a coating layer on the inner surface of the plunger.

6. The plunger assembly according to claim 5, wherein the coating layer has a thickness of at least 3 microns.

7. The plunger assembly according to claim 5 or 6, wherein the coating layer has a thickness of more than 0% to 75% or less of the total thickness of the plunger.

8. The plunger assembly according to claim 5 or 6, wherein the coating layer has a thickness of about 25 microns to about 200 microns.

9. The plunger assembly according to any one of claims 5 to 8, wherein the coating layer is thermoformed on the plunger.

10. The plunger assembly according to any one of claims 5 to 8, wherein the coating layer is spray-coated onto the plunger.

11. The plunger assembly according to claim 10, wherein the coating is spray-coated onto the plunger and then photocured.

12. The plunger assembly according to claim 3 or 4, wherein the biocompatible polymer is dispersed within the elastic material.

13. The plunger assembly according to claim 12, wherein the biocompatible polymer is scattered within the elastic material on the inner surface of the plunger, forming a scattered polymer layer.

14. The plunger assembly according to claim 13, wherein the scattered polymer layers contain more than 0% to 100% by weight of the biocompatible polymer based on the total weight of the scattered polymer layers.

15. The aforementioned elastic material has a glass transition temperature T of -80°C or lower. ｇ A plunger assembly according to any one of the prior claims, having the following features.

16. The aforementioned elastic material has a glass transition temperature T of -120°C or higher. ｇ A plunger assembly according to any one of the prior claims, having the following features.

17. The aforementioned elastic material has a glass transition temperature T of -65°C or lower. ｇ A plunger assembly according to any one of the prior claims, comprising a silicone rubber having

18. A pharmaceutical container assembly, A pharmaceutical container comprising a body having an outer surface and an inner surface, The body comprises a plunger inserted into the opening of the main body, The radial outer surface of the plunger forms an interference fit with the inner surface of the main body. The plunger has a glass transition temperature T of -65°C or lower. ｇ Includes an elastic material having The aforementioned interlocking fit forms a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The seal is maintained when the pharmaceutical container assembly is cooled to -65°C or below.

19. The helium leakage rate of the sealed container is 1.4 × 10⁻⁶ at a temperature of -65°C. －６ cm ３ The pharmaceutical container assembly according to claim 18, wherein the value is less than or equal to / s.

20. The pharmaceutical container assembly according to claim 18 or 19, wherein the interference fit is at least 2%, and the interference fit percentage is the percentage difference between the diameter of the radial outer surface of the plunger and the diameter of the inner surface of the body.

21. The pharmaceutical container assembly according to any one of claims 18 to 20, wherein the aforementioned interference fit is at least 5%.

22. The pharmaceutical container assembly according to any one of claims 18 to 21, wherein the plunger further comprises a biocompatible polymer.

23. The pharmaceutical container assembly according to claim 22, wherein the biocompatible polymer comprises one or more of butyl rubber, bromobutyl rubber, chlorobutyl rubber, polytetrafluoroethylene, ethylenetetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxyalkane, and copolymers or blends thereof.

24. The pharmaceutical container assembly according to claim 22 or 23, wherein the biocompatible polymer forms a coating layer on the inner surface of the plunger.

25. The pharmaceutical container assembly according to claim 24, wherein the coating layer has a thickness of at least 3 microns.

26. The pharmaceutical container assembly according to claim 24 or 25, wherein the coating layer has a thickness of more than 0% to 75% or less of the total thickness of the plunger.

27. The pharmaceutical container assembly according to claim 24 or 25, wherein the coating layer has a thickness of about 25 microns to about 200 microns.

28. The pharmaceutical container assembly according to any one of claims 24 to 27, wherein the coating layer is thermoformed on the plunger.

29. The pharmaceutical container assembly according to any one of claims 24 to 27, wherein the coating layer is spray-coated onto the plunger.

30. The pharmaceutical container assembly according to claim 29, wherein the coating is spray-coated onto the plunger and then photocured.

31. The pharmaceutical container assembly according to claim 22 or 23, wherein the biocompatible polymer is dispersed within the elastic material.

32. The pharmaceutical container assembly according to claim 31, wherein the biocompatible polymer is scattered within the elastic material on the inner surface of the plunger, forming a scattered polymer layer.

33. The pharmaceutical container assembly according to claim 32, wherein the scattered polymer layer comprises more than 0% to 100% by weight of the biocompatible polymer based on the total weight of the scattered polymer layer.

34. The aforementioned elastic material has a glass transition temperature T of -80°C or lower. ｇ A pharmaceutical container assembly according to any one of claims 18 to 33, comprising:

35. The elastic material has a glass transition temperature T of -120°C or higher. ｇ The pharmaceutical container assembly according to any one of claims 18 to 34.

36. The aforementioned elastic material has a glass transition temperature T of -65°C or lower. ｇ A pharmaceutical container assembly according to any one of claims 18 to 35, comprising a silicone rubber having the properties of a silicone rubber.

37. The pharmaceutical container assembly according to any one of claims 18 to 36, wherein the body of the pharmaceutical container comprises glass or polymer glass.

38. The pharmaceutical container assembly according to any one of claims 18 to 37, wherein the seal is maintained when the container is cooled to -80°C or below.

39. The pharmaceutical container assembly according to any one of claims 18 to 38, wherein the seal is maintained when the container is cooled to -120°C or below.

40. The pharmaceutical container assembly according to any one of claims 18 to 39, wherein the pharmaceutical container is a syringe.

41. The pharmaceutical container assembly according to any one of claims 18 to 39, wherein the pharmaceutical container is a cartridge.

42. A method for storing a pharmaceutical composition, wherein the method is To provide a pharmaceutical container assembly, the pharmaceutical container assembly is A pharmaceutical container comprising a body having an outer surface and an inner surface, The body comprises a plunger inserted into the opening of the main body, The radial outer surface of the plunger forms an interference fit with the inner surface of the main body. The aforementioned interlocking fit forms a seal between the inner surface of the body of the pharmaceutical container and the outer surface of the plunger. The plunger is provided to include an elastic material having a glass transition temperature of -65°C or lower. Adding a biological composition or pharmaceutical composition to the aforementioned pharmaceutical container, Inserting the plunger into the pharmaceutical container, The process includes cooling the pharmaceutical container assembly and the biological composition or pharmaceutical composition disposed within the pharmaceutical container assembly to a temperature below -65°C. A method wherein the seal is maintained when the pharmaceutical container assembly is cooled to -65°C or below.

43. The method according to claim 42, wherein the biological composition or pharmaceutical composition is added to the pharmaceutical container before the plunger is inserted into the pharmaceutical container.

44. The method according to claim 42, wherein the biological composition or pharmaceutical composition is added to the pharmaceutical container after the plunger has been inserted into the pharmaceutical container.

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