Medicament container, injection device and method of storing or preserving of a medicament in a medicament container

Abstract

In one aspect the present disclosure relates to medicament container (10) comprising: - a barrel (11) with a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), - an outlet (14) at the distal end (15), - a stopper (20) located inside the barrel (11), sealing the barrel (11) towards the proximal end (16) and movable relative to the barrel (11) to expel a medicament (8) through the outlet (14), - a proximal fastening structure (18) at the proximal end (16), and - a hermetic closure (30) at the proximal end (16) to hermetically seal the proximal end (16).

Description

[0001] Title

[0002] Medicament Container, Injection Device and Method of Storing or Preserving of a Medicament in a Medicament Container

[0003] Description

[0004] Field

[0005] The present disclosure relates to the field of medical devices, particularly to injection devices, such as syringes and in particular to prefilled syringes. In a further aspect the present disclosure relates to the filling of pre-filled medicament containers or pre-filled injection devices. In a further aspect the present disclosure relates to aseptic medicament containers configured for storage at low temperatures, ultra-low temperatures or cryogenic temperatures and to a method of preparing such medicament containers.

[0006] Background

[0007] Drug delivery devices for setting and dispensing a single or multiple doses of a liquid medicament are as such well-known in the art. Generally, such devices have substantially a similar purpose as that of an ordinary syringe.

[0008] Drug delivery devices, such as pen-type injectors, have to meet a number of user-specific requirements. For instance, with patients suffering chronic diseases, such as diabetes, the patient may be physically infirm and may also have impaired vision. Suitable drug delivery devices especially intended for home medication therefore need to be robust in construction and should be easy to use. Furthermore, manipulation and general handling of the device and its components should be intelligible and easy understandable. Such injection devices should provide setting and subsequent dispensing of a dose of a medicament of equal or variable size. Moreover, a dose setting as well as a dose dispensing procedure must be easy to operate and has to be unambiguous.

[0009] Some drug delivery or injection devices provide selecting of a dose of a medicament of variable size and subsequent injecting of the dose previously set. Other injection devices provide setting and dispensing of a fixed dose. Here, the amount of medicament that should be injected in accordance to a given prescription schedule is always the same and does not change or cannot be changed over time.

[0010] Some injection devices are implemented as reusable injection devices offering a user to replace a medicament container, such as a cartridge. Other injection devices are implemented as a disposable injection device. With disposable injection devices it is intended to discard the entirety of the injection device when the content, i.e. the medicament, has been used up. Disposable injection devices may be prefilled with the injectable medicament.

[0011] Medical devices, such as drug delivery devices or injection devices may have a limited lifetime. Due to regulatory provisions or for reasons of patient safety, medical devices or drug delivery devices may only be used for a rather limited number of times. Also, some medical devices, drug delivery devices or injection devices or parts thereof may be intended only for a one-time use. They may be designed or constructed as disposable devices or device components, which are intended to be discarded after use.

[0012] Some medicament to be injected or delivered by injection devices may require a relatively low storage temperature during storage and / or shipment. Some medicaments, e.g. vaccines or the like pharmaceutical products may require storage below -60°C. Typically, and up to now, such medicaments can only be stored and provided in vials. This requires a rather elaborate preparation of the medicament for extracting one of numerous doses of medicament from a respective vial.

[0013] Therefore, it would be beneficial to provide an improvement for administration of medicaments to users by way of injection, wherein the medicament has to be stored at ultra-low temperatures, e.g. below minus 60°C or even below minus 135°C.

[0014] Generally, single doses of a medicament can be provided or injected by making use of pre-filled injection devices, such as a pre-filled pen injectors or pre-filled syringes. Here, a stopper or piston sealing a barrel of a medicament container has to be moved, e.g. in a distal direction for expelling the dose of the medicament from the respective medicament container. The requirement of a stopper movable relative to a barrel may be rather crucial to maintain a container closure integrity especially at ultra-low temperatures during storage and / or shipment.

[0015] Moreover, filling of such pre-filled syringes or injection devices is quite elaborate and cumbersome, especially when the filling process should be conducted under aseptic conditions. Hence, filling of a respective medicament container has to be conducted in a rather clean and / or sterile environment. At the same time the pharmaceutical product to be filled into the medicament container should not or must not get in contact with any component or substances that may contaminate the medicinal or pharmaceutical products.

[0016] Additionally, barrels of medicament containers, e.g., of pre-filled syringes can be made of a vitreous material, e.g. glass, and the stopper can be made of an elastomeric material. For this material combination an intact closure integrity between the barrel and the stopper may be difficult to maintain when exposed to particularly low temperatures or ultralow temperatures. The materials of the barrel and the movable stopper exhibit different coefficients of thermal expansion or contraction, which might lead to an insufficient closure integrity when exposing the medicament container or pre-field syringe to comparatively low temperatures, such as ultralow temperatures in the region of - 80°C and dry ice transport. Moreover, the medicament inside the barrel may be subject to thermal expansion or contraction and may thus induce a limited movement of the stopper, which movement may be also detrimental to the maintenance of the container closure integrity. Multiple thermal cycles of freezing and thawing, different storage conditions, and temperature excursion are possible during finish, transport, storage, or manipulation.

[0017] Even though use of a plastic material for the barrel of the medicament container may provide a better performance at ultralow temperatures because the coefficient of thermal expansion of the respective materials used for the barrel on the one hand side and used for the stopper on the other hand side may help to ensure or to provide an improvement to the container closure integrity at the interfaces between the barrel and the stopper. However, such a system has not shown yet to provide a satisfying sealing performance at ultralow temperatures.

[0018] It is therefore desirable to provide an improved medicament container for cryopreservation of a medicament, wherein the container may at the same time provide an effective tool to expel the medicament from the container. It is a particular aim to provide improvements to pre-filled syringes and to provide a solution to store a medicament inside a pre-filled syringe even at ultralow temperatures or at cryopreservation temperatures.

[0019] It is a particular aim to maintain and to improve a double function of the stopper of the medicament container. The stopper should provide a rather smooth displacement for or during expelling of the medicament. It should further provide a sufficient container closure integrity during storage until administering of the medicament. However, increasing the tightness of the interface between the barrel and the stopper might be detrimental for the movement of the stopper during or for injection of the medicament. Summary

[0020] The above-mentioned drawbacks will be solved by a medicament container, by an injection device and by way of a method of cryopreservation of a medicament as defined by the features of the independent claims. Numerous examples and embodiments of the solutions are subject matter of respective dependent claims.

[0021] In one aspect there is provided a medicament container. The medicament container comprises a barrel. The barrel comprises a barrel sidewall. The barrel sidewall may be of tubular shape or cylindrical geometry. The barrel defines a longitudinal direction. Typically, the longitudinal direction coincides with a central or longitudinal axis of the barrel or of the barrel cylinder. The barrel comprises a distal end and a proximal end opposite the distal end. The distal end is a longitudinal distal end. The proximal end is a longitudinal proximal end.

[0022] The medicament container and hence the barrel comprises an outlet at the distal end of the barrel. The medicament container further comprises a stopper. The stopper is located inside the barrel. The stopper is configured and shaped to seal the barrel towards the proximal end. The stopper is movable relative to the barrel, e.g. slidably movable along the longitudinal direction relative to the barrel. The stopper is particularly movable relative to the barrel to expel a medicament through the outlet.

[0023] The medicament container is particularly suitable to store or to contain a medicament, e.g., a liquid medicament, between the distally located outlet and the stopper. By moving the stopper in distal direction relative to the barrel the medicament can be expelled through the outlet of the barrel.

[0024] The medicament container further comprises a hermetic closure at the proximal end to hermetically seal the proximal end. By way of the hermetic closure, the proximal end of the barrel can be hermetically sealed against the environment. In this way, the proximal end and hence the interior of the barrel between the proximal end and the stopper can be effectively protected against environmental influences and a potential contamination in case that the container closure integrity provided by the stopper in sliding engagement or in sealing engagement with an inside surface of the barrel should be insufficient or should become insufficient, e.g., at ultralow temperatures.

[0025] Specifically, the hermetic closure is configured to persistently and to permanently hermetically seal the proximal end of the barrel. In this way an at least temporary insufficient container closure integrity in the interface between the stopper and the barrel may become tolerable. Such an insufficiency may arise when the medicament container is subject to cryopreservation or when the medicament container is cooled down to a cryopreservation temperature, e.g., to an ultralow temperature, such as below -60°, below -80°C, below -120°C or even below -160°C.

[0026] Hence, the hermetic closure as provided at the proximal end of the barrel of the medicament container may serve to maintain a sufficient container closure integrity even at ultralow temperatures. Insofar, any insufficiencies or drawbacks in the interface between the stopper and the barrel at ultralow temperatures or at cryopreservation temperatures can be effectively compensated by the hermetic closure.

[0027] Typically, the hermetic closure is attached or engaged with the proximal end under aseptic conditions, under which conditions the filling of the interior of the barrel with the medicament is also conducted.

[0028] In this way it can be ensured, that the interior of the barrel between the stopper and the hermetic closure is void and remains void of any contaminant. A temporary insufficient container closure integrity in the region of the stopper and the respective inside of the sidewall of the barrel can be tolerated. The hermetic closure as provided at the proximal end of the barrel effectively serves to prevent ingress of any contaminants or any other harmful substances that could be detrimental to the long-term storage of the medicament located between the outlet and the stopper.

[0029] According to some examples, the hermetic closure is void of any through openings or through recesses.

[0030] According to a further example the proximal end of the barrel is provided with a proximal fastening structure. The hermetic closure is configured to engage with the proximal fastening structure to hermetically seal the proximal end of the barrel.

[0031] The proximal fastening structure as provided at the proximal end of the barrel may provide a well-defined attachment, fixing and sealing of the proximal end by way of the hermetic closure. The hermetic closure may be provided or equipped with a complementary shaped counter fastening structure to sealingly engage and / or to hermetically engage with the proximal fastening structure at the proximal end of the barrel of the medicament container.

[0032] According to some examples the hermetic closure may be detachably connectable or fixable to the proximal end of the barrel of the medicament container. In this way and after cryopreservation and thawing to room temperature and hence before use of the medicament container for injecting or expelling of the medicament, the hermetic closure may be disconnected or detached from the proximal end thus allowing to provide access to the stopper. It may be then that the stopper is connected to a separate plunger by way of which the medicament container may transform or transition into an injection device.

[0033] By attaching or engaging a plunger to the stopper the stopper can be moved relative to the barrel, e.g., in distal direction through interaction with the plunger. In some examples the plunger may be attached or maybe simply brought in longitudinal abutment with a proximal side or proximal face of the stopper. In this way, the plunger can be used to exert a distally directed thrust onto the stopper, which thrust or force effect is sufficient to move or to displace the stopper relative to the barrel in distal direction. By such a distally directed movement of the stopper relative to the barrel an amount or the entirety of the medicament located between the stopper and the outlet of the barrel can be expelled through the outlet.

[0034] According to some examples the hermetic closure provides a backup closure system for the medicament container. It provides a supplemental closure for hermetically sealing the interior of the barrel towards the proximal end or towards the proximal direction of the barrel.

[0035] By way of the hermetic closure at the proximal end of the barrel the medicament container can be reliably sealed for storage, transportation and preservation at ultralow temperatures or at cryopreservation temperatures. A potential lack or insufficiency of a closure integrity between the stopper and the barrel may be compensated and counterbalanced by the hermetic closure at the proximal end of the barrel. This way, ingress of contaminants into the medicament storage space as confined by the barrel, the outlet and the stopper, can be effectively prevented.

[0036] According to a further example the hermetic closure comprises a sealing member and a retainer. The sealing member is configured to sealingly engage with the proximal end of the barrel. The retainer is configured to fix and / or to fasten the sealing member to the proximal end. In some examples the sealing member and the retainer are separate parts. The sealing member may comprise one of a sealing disc, a sealing ring and a sealing stopper to engage with at least one of an inside surface of the sidewall of the barrel at the proximal end of the barrel, to engage with a proximal end face of the barrel and / or to engage with an outside surface of the barrel at the proximal end. In either way the sealing member and the retainer as well as the proximal fastening structure of the barrel or barrel sidewall are shaped to provide a permanent hermetic seal at the proximal end of the barrel, which is configured to withstand and / or to cope with comparatively low temperatures, e.g. of ultralow temperatures or cryopreservation temperatures.

[0037] According to some examples, the sealing member and / or the retainer is void of any through openings or through recesses.

[0038] According to some examples and in the context of the present disclosure ultralow temperatures may range between minus 60°C and minus 85 °C. Cryogenic temperatures may range between minus 135°C and minus 196°C.

[0039] According to some examples the sealing member is detachably connectable or detachably fixable to the proximal end of the barrel of the medicament container, e.g. by way of the retainer. In this way and after cryopreservation and thawing to room temperature and hence before use of the medicament container for injecting or expelling of the medicament, in a first step, the retainer can be disconnected or detached from the proximal end thus allowing to detach, e.g. to restlessly and / or to completely detach the sealing member from the proximal end of the barrel in a subsequent second step, e.g., to provide unhindered access to the stopper.

[0040] In some examples, detaching of the retainer from the proximal end of the barrel may come along with an automatic detaching of the sealing member from the proximal end of the barrel. Here, the sealing member may be and / or may remain connected to them retainer upon detachment from the proximal end of the barrel.

[0041] According to some examples the sealing member comprises a body made of elastomeric material. The sealing member may consist of an elastomeric material, which is particularly suitable to provide a good, persistent and sufficient hermetic seal at the proximal end of the barrel. In further examples the sealing member comprises a thermoplastic material, which is likewise suitable to seal the proximal end of the barrel.

[0042] The retainer is configured to permanently attach and / or to permanently fix the sealing member to the proximal end. Typically, the retainer is configured to keep the sealing member in sealing contact, e.g., in a hermetically sealing contact with the proximal end of the barrel. In this way, the retainer serves to provide and / or to maintain a sufficient hermetically sealing effect of the sealing member at the proximal end of the barrel or barrel sidewall. According to a further example the retainer comprises a cup-shaped cap portion comprising a sidewall and a bottom to at least partially enclose at least a portion of the sealing member. By at least partially or by entirely enclosing the sealing member, the retainer may provide or improve mechanical stability of the sealing member and / or to keep the sealing member in a sealing configuration with the proximal end of the barrel. By way of a cup - shaped cap portion it may be also possible to enclose at least portions of the proximal fastening structure inside the receptacle formed by the sidewall and the bottom of the retainer.

[0043] Hence, the sidewall and the bottom of the cup-shaped cap portion of the retainer may be sized and configured to receive both, the proximal fastening structure at the proximal end of the barrel and the sealing member in engagement with the proximal end and / or in engagement with the proximal fastening structure of the barrel sidewall at the proximal end of the barrel. In this way and by receiving both, the proximal fastening structure of the barrel and / or by receiving at least a portion, e.g., an outer edge portion of the sealing member, the sealing member can be kept in sealing engagement with the proximal end and / or with the proximal fastening structure through interaction and / or through a holding force as applied by the retainer, e.g. as applied by a sidewall of the retainer, which may positively or frictional ly engage with at least one of the proximal fastening structure of the barrel and the sealing member.

[0044] According to a further example the retainer comprises a counter fastening structure, which is complementary shaped to the proximal fastening structure as provided at the proximal end of the barrel sidewall. By providing mutually corresponding structures at the retainer and at the proximal end of the barrel the retainer can be fastened to the proximal end of the barrel in a well-defined and failure safe manner. This provides a rather easy, well-defined, long-lasting and durable fixing of the sealing member to the proximal end of the barrel.

[0045] According to a further example the counter fastening structure of the retainer is provided on or in the sidewall of the cup - shaped cap portion of the retainer. In some examples the counter fastening structure may be provided on an inside surface of the sidewall of the cap portion. Then, the proximal fastening structure may be provided on an outside of the sidewall of the barrel at the proximal end of the barrel. In other examples the counter fastening structure may be provided on an outside surface of the sidewall of the cup-shaped cap portion of the retainer. It may be then that the proximal fastening structure as provided at the proximal end of the barrel is located or provided at an inside surface of the barrel sidewall. In this way, there can be provided a kind of an interleaved or telescopically engaged interface between the retainer and the proximal fastening structure of the barrel. Hence, by fastening or fixing the retainer to the proximal fastening structure the retainer and the proximal end of the barrel sidewall of the barrel may mutually mechanically stabilize, e.g., in the course of engaging the proximal fastening structure with the counter fastening structure of the retainer. The sealing member may be located between the fastening structure and the counter fastening structure. In other examples the sealing member may be located longitudinally between the bottom of the cap portion of the retainer and a proximal end face of the barrel sidewall of the barrel when the proximal fastening structure and the counter fastening structure are mutually engaged. It may be also provided that the sealing member is compressed or squeezed in the course of engaging the proximal fastening structure with the counter fastening structure, e.g., in the course of fastening or fixing the retainer to the proximal end of the barrel. In this way, a sealing effect or sealing capability of the sealing member can be even improved.

[0046] It may be also provided that the sealing member is and remains squeezed or compressed when the retainer is fixed to the proximal fastening structure of the barrel sidewall.

[0047] According to a further example the retainer comprises a crimped cap or a crimpable cap to positively engage with the proximal fastening structure. The crimped cap or crimpable cap may comprise or may be made of a plastically deformable material. The crimped cap or crimpable cap may be plastically deformable to engage with both, the proximal fastening structure at the proximal end of the barrel and with the sealing member. By way of a plastic deformation of the crimped cap or crimpable cap the sealing member can be held and fixed in a hermetic sealing configuration at the proximal end of the barrel or barrel sidewall.

[0048] According to some examples the crimped cap may provide a compression or press fit of the sealing member to the proximal end of the barrel. In this way, the crimped cap may be configured to provide or to apply a compressive force onto the sealing member to keep the sealing member in a permanent or persistent hermetic sealing engagement with the proximal end of the barrel.

[0049] According to a further example the retainer comprises a predetermined breaking structure and a tear-off portion to disintegrate the retainer. By way of the tear-off portion a user may apply a respective and well-defined force effect onto or into the retainer under which effect the predetermined breaking structure starts to disintegrate. In this way, the tear-off portion provides a well-defined disintegration of the retainer. The tear-off portion, which may be manually grippable by a user of the medicament container, serves to provide a well-defined disintegration or transferring of the retainer into a release configuration, in which the retainer no longer provides a fixing of the sealing member to the proximal end. Hence, by way of the predetermined breaking structure and the tear-off portion the retainer can be detached or released from the proximal end and hence from the proximal fastening structure of the barrel of the medicament container. The tear-off portion and the predetermined breaking structure of the retainer provide a well-defined detachment of the hermetic closure from the proximal end of the barrel of the medicament container. Such a detachment may be of particular benefit after a cryopreservation of the medicament container and immediate before use of the medicament container in the process of expelling or injecting of the medicament from the medicament container.

[0050] According to a further example at least a portion of the retainer is covered by a cover. By way of a cover, e.g. a plastic cover or molded cover, the predetermined breaking structure and / or the tear-off portion can be protected against misuse or inadvertent use or actuation.

[0051] Moreover, by way of the cover, the retainer itself can be protected against mechanical impact or environmental influences.

[0052] In addition, the cover may provide an identification or a visually distinguishing feature of the medicament container. Hence, the cover may be provided in different or characteristic colors to distinguish the medicament container provided with a cover of a first color from a medicament container provided with a cover of a second color, that distinguishes from the first color.

[0053] For detaching or for and disconnecting the hermetic closure from the barrel it may be required to initially remove the cover, e.g., to separate the cover from the retainer to gain access to the tear-off portion. In a second step the user may then grip or actuate the tear-off portion to disintegrate the predetermined breaking structure of the retainer. The retainer may be then transferred into a disintegrated state, in which it does no longer provide a fixing or fastening of the sealing member to the proximal end of the barrel.

[0054] According to another example the proximal fastening structure comprises one of a barrel flange and a collar protruding radially outwardly from the sidewall of the barrel. In some examples the sidewall of the barrel is of tubular shape. Accordingly, the barrel flange or collar may comprise an annularly shaped structure, which may protrude radially outwardly from an outside surface of the sidewall at the proximal end of the sidewall. In other examples only portions of the outer circumference of the sidewall of the barrel are provided with a barrel flange or barrel flange portion. In some examples the barrel flange may comprise a first barrel flange portion and a second barrel flange portion protruding from diametrically opposite outside sections of the sidewall of the barrel.

[0055] In either way, the radially outwardly protruding barrel flange provides or forms the proximal fastening structure which may easily engaged with the retainer for fastening the retainer and / or the sealing member to the proximal fastening structure, hence, to the barrel flange.

[0056] In some examples the barrel flange and the sidewall of the barrel are integrally formed. The barrel flange and the sidewall may be implemented as a component or sections of a single pieced barrel.

[0057] According to some examples the barrel is a molded body. The barrel may be made of a vitreous material, e.g. glass. It may be also made of a plastic material, e.g., cyclic olefin copolymer (COC) or cycloolefin polymer (COP).

[0058] According to a further example and when the retainer comprises a crimped or crimpable cap the retainer is positively engaged or is positively engageable with the barrel flange. The crimped cap may be arranged or attached onto the barrel flange with the sealing member located inside the cup - shaped receptacle of the crimped cap. It may be then due to a plastic deformation, e.g., of the sidewall of the crimped cap, that a portion of the sidewall of the crimped cap is deformed radially inwardly to grip under a recessed section of the barrel flange facing in distal direction.

[0059] In this way, an outside edge of the barrel flange can be enclosed and covered by the crimped cap. By way of the radially outwardly extending structure or geometry of the barrel flange there can be provided an effective proximal fastening structure to positively engage with the plastically deformed crimped cap or crimpable cap.

[0060] According to a further example the barrel is of substantially tubular shape and transitions into a radially narrowing shoulder portion, which is followed by a radially narrowed neck portion towards the proximal end of the barrel. The narrowing shoulder portion is at least provided on the outside of the barrel. The narrowing shoulder portion merges in proximal direction and hence towards the proximal end of the sidewall into the radially narrowed neck portion.

[0061] By providing a radially narrowed neck portion at or near the proximal end of the barrel there can be provided a rather distinct and characteristic barrel flange. Hence, the undercut as provided at the distal side of the barrel flange can be increased and there can be provided an improved mechanical engagement between the barrel flange and the retainer. Moreover, and in some examples also the inside surface of the sidewall of the barrel may comprise the radially narrowing shoulder and the radially narrowed neck portion compared to the tubular part of the sidewall, which is located distally from the radially narrowed shoulder.

[0062] In either way and by providing the radially narrowed neck portion, which in proximal direction may further merge into the radially widened barrel flange, a radial recess and hence a radial extent between an outside edge of the barrel flange and the radially narrowed neck can be increased compared to a solution or implementation of the barrel, where the barrel flange extends radially outwardly from the tubularly-shaped or cylindrically - shaped barrel sidewall.

[0063] By providing a radially narrowed neck portion in the barrel sidewall distally adjacent to the barrel flange there can be provided an improvement for the fixing of the crimped or crimpable cap and hence for any kind of retainer configured to positively engage with the barrel flange. This effect may be obtained without the necessity to increase the overall radial dimensions of the barrel flange compared to a cylindrical or tubular implementation of the proximal end of the barrel sidewall.

[0064] According to another example the retainer comprises a first retainer part and a second retainer part. The first retainer part and the second retainer part each comprise a receptacle, which is sized and configured to receive at least a portion of the barrel flange and a portion of the sealing member, which is in longitudinal abutment with the barrel flange.

[0065] According to some examples the sealing member may comprise a sealing disc to be arranged in direct longitudinal or axial abutment with a proximal side of the barrel flange. In further examples the sealing member comprises a sealing stopper comprising an insert portion, which is sized to become inserted into the interior of the barrel at the proximal end of the barrel. The insert portion may comprise an outward facing sidewall to engage, e.g., to hermetically and / or sealingly engage with an inside surface of the barrel sidewall at the proximal end of the barrel.

[0066] In some examples the sealing member comprises both, a sealing disc and an insert portion. Here, the insert portion may comprise a diameter or cross-section that is smaller than a respective diameter or cross-section of the sealing disc. The sealing disc may at the same time provide a kind of a flange for the insert portion. The sealing disc section of the sealing member may be provided at the proximal end of the insert portion. The distal portion and the insert portion of the sealing member may be unitarily shaped. They may be part of a single or unitary sealing member, e.g., made of an elastomeric material, such as synthetic or natural rubber. Here and with the retainer comprising first and second retainer part, the first and the second retainer part may be sized and shaped to receive both, at least a portion of the barrel flange and a portion of a sealing disc or flange portion of the sealing member when in an assembly configuration. The receptacle of the first retainer part and the receptacle of the second retainer part may be open towards a radial inside facing the radial direction with regards to the geometry of the barrel. This allows to assemble the first retainer part and the second retainer part from opposite radial sides onto the barrel flange and the sealing member attached to the barrel flange.

[0067] In some examples the sealing member may be attached or engaged with the proximal end of the barrel by bringing the sealing member in longitudinal, e.g. distally directed abutment with the proximal end of the barrel sidewall, e.g., with the proximal end or proximal side of the barrel flange. It may be then that the first retainer part and the second retainer part are attached with their respective receptacle to the mutual assembly of the sealing member and the barrel flange. Here, the first and second retainer part may be attached to the pre-assembly of the sealing member and the barrel flange according to a radial inwardly directed fastening or mounting direction.

[0068] The receptacle or receptacles of the first and the second retainer part may be sized to receive both, the barrel flange and at least a portion of the sealing member in longitudinal abutment with the barrel flange. The receptacle(s) may be sized to compress or to at least slightly compress the sealing member in distal direction to the barrel flange.

[0069] According to some examples the first retainer part and the second retainer part are provided or are assembled to diametrically opposite sides of the barrel flange or oppositely located barrel flange portions. In this way, there can be provided a twofold fastening and fixing of the sealing member to the barrel flange. It is even conceivable that the retainer comprises even more retainer parts, e.g. three retainer parts or four retainer parts. The numerous retainer parts may be arranged circumferentially around the circular shaped barrel flange or around the circumference of the outside of the barrel sidewall at the proximal end of the barrel.

[0070] According to a further example the sealing member comprises a flange portion in longitudinal abutment with the barrel flange. The receptacle of the first retainer part and / or the receptacle of the second retainer part are e.g. confined by a sidewall, by a bottom portion and by an upper portion. A size of an aperture of the receptacle between the bottom portion and the upper portion is less than or equal to a combined longitudinal extent of the barrel flange and the flange portion of the sealing member. In this way the flange portion of the sealing member can be firmly held or fixed in longitudinal abutment with the barrel flange by attaching the first retainer part and the second retainer part to respective portions of the barrel flange in accordance to a radially inwardly directed fastening or assembly process of the first and / or second retainer parts.

[0071] In some examples and when the longitudinal size of the aperture as defined by the bottom portion and the upper portion of the receptacle of the first and / or second retainer parts is slightly less than a combined longitudinal extent of the barrel flange and the flange portion of the sealing member it may be required that the flange portion of the sealing member is at least slightly squeezed or compressed in longitudinal direction to fit into the receptacle as provided by the first and / or second retainer parts.

[0072] According to a further example the first retainer part is engageable with a first barrel flange portion of the barrel flange. The second retainer part is engageable with a second barrel flange portion of the barrel flange. The second barrel flange portion may be located circumferentially offset from the first barrel flange portion. The first barrel flange portion and the second barrel flange portion may be provided at diametrically opposite circumferential positions of the proximal end of the barrel sidewall. In this way and by providing first and second barrel flange portions there may be provided a syringe - like flange configuration, which is configured to provide an immediate support for an index finger and a middle finger of a user for holding the medicament container during an / or for expelling of the medicament through the outlet.

[0073] According to a further example the medicament container comprises a fixing element with a first counter fastener and with a second counter fastener. The first retainer part comprises a first fastener to engage with a first counter fastener and the second retainer part comprises a second fastener to engage with the second counter fastener. By way of the fixing element the first and the second retainer parts can be kept in a final assembly configuration. They may be fixable relative to each other at least with regard to the radial and / or circumferential direction by way of the fixing element.

[0074] The first and second retainer parts may be fixable in longitudinal direction to the barrel flange and / or to the sealing member through their respective receptacle(s) that engages with the barrel flange and with the sealing member, which is in abutment with the barrel flange. By way of the fixing element the first and second retainer parts can be kept in a final assembly configuration.

[0075] The fixing element may be implemented as a frangible fixing element. It may comprise a predetermined breaking structure by way of which the fixing element may be disintegrated into two parts. Here, and in this way each part may remain connected or fastened to first and second fasteners of first and second retainer part, respectively. In this way and by disintegrating the fixing element the first and the second retainer parts may be moved radially outwardly relative to each other thereby disengaging from the barrel flange and / or disengaging from the sealing member. In this way, and after detaching first and second retainer parts from the proximal end of the barrel and / or from the sealing member it may be easily detached from the proximal end of the barrel.

[0076] It may be then that there is provided access to the stopper, e.g. by way of a plunger, which is sized for insertion into the interior of the barrel from the proximal end of the barrel.

[0077] According to a further example the fixing element comprises a fixing disc. The first counter fastener and the second counter fastener each comprise an aperture extending through the fixing disc or the first and second counter fastener each comprise a recess provided in the fixing disc. The recess or aperture as provided by first and second counter fasteners in the fixing disc may be movable relative to each other. It may be upon final assembly and after first and second retainer parts have reached their final assembly configuration that the first and second fasteners arrive in a mutual distance that matches the distance or configuration of the first and second counter fastener in or on the fixing disc.

[0078] The fixing disc may be simply attached to the proximal end of the medicament container. Here, the first and second fasteners as provided on or at the first and second retainer parts may be accessible from the proximal end of the medicament container. A mutual fixing between the first and the second retainer parts may be easily obtained by attaching the fixing disc to the first and second container parts.

[0079] According to a further example the first fastener and / or the second fastener comprises a projection configured for insertion into or through the aperture of at least one of the first counter fastener and the second counter fastener. Hence, the first fastener may comprise a first projection, e.g., a pin-like projection protruding proximally from an end face of the first retainer part. Likewise, the second fastener of the second retainer part may comprise an identically or similarly shaped projection protruding proximally from an end face of the second retainer part. The end faces of the first and second retainer parts may be provided on an outside surface of the bottom portion confining the receptacle.

[0080] According to a further example it may be the first and / or the second counter fastener that comprises a longitudinally extending projection to engage with an aperture or recess as provided by the first and / or the second fastener.

[0081] In further examples it may be provided that the first fastener comprises one of a longitudinal projection and a recess or through opening and that the second fastener comprises another one of a longitudinal projection and a through opening. Also here, first and second fasteners are complementary shaped to respective counter fasteners as provided by the fixing element.

[0082] By way of a longitudinally extending projection provided with one of the first and second fasteners complementary shaped to a respective recess or through opening as provided on one of the first and second counter fasteners there can be provided a mutual fixing of first and second retainer parts by way of the fixing element in a final assembly configuration, in which the barrel flange and the flange portion of the sealing member are permanently attached to each other in longitudinal direction, since they are firmly held inside the receptacle.

[0083] According to a further example the outlet of the medicament container comprises a nozzle. The outlet may further comprise a connector for at least one of an infusion line or for a needle. The connector may be implemented as a standardized fluid transferring connector, such as one of a male or female Luer-type connector.

[0084] The nozzle and hence the outlet of the medicament container may be sealed by a protective cap or by an outlet cap. In this way, the outlet may be also hermetically sealed and may be thus protected against ingress of any contaminants or the like substances.

[0085] According to a further example the outlet is provided with an injection needle extending into an interior of the barrel of the medicament container. The injection needle may be integrated into the outlet. The injection needle may form or constitute the outlet. The injection needle may be molded or staked in the distal end of the barrel or barrel sidewall. The barrel sidewall may terminate or may taper into the nozzle towards the distal end. Likewise, also the injection needle, e.g. a tipped end of the injection needle may be covered or provided with a protective cap by way of which the outlet or distal end of the needle can be also hermetically sealed against ingress of any contaminants or the like components or substances.

[0086] According to a further example the proximal fastening structure comprises a threaded section to engage with a complementary shaped counter threaded section of the hermetic closure and / or of the retainer. Here, the retainer may comprise a cup-like shaped receptacle or a cap - shaped cap portion configured for threaded engagement with the proximal fastening structure as provided at the proximal end of the barrel. In some examples an open-ended proximal end of the barrel can be effectively closed and / or sealed by the hermetic closure by threadedly engaging the retainer to the proximal fastening structure, hence by threadedly engaging the counter threaded section of the retainer with the threaded section of the proximal fastening structure.

[0087] A threaded engagement between the retainer and the proximal fastening structure provides a rather efficient and intuitive solution to detachably connect and / or to detachably fix the hermetic closure to the proximal end of the barrel. Insofar, and for administering the medicament or for preparing the medicament for administration the hermetic closure can be rather easily detached or disconnected from the proximal end by unscrewing the retainer from the threaded section of the proximal fastening structure.

[0088] According to some examples the sidewall of the proximal end of the barrel comprises the threaded section to engage with the complementary shaped counter threaded section of the retainer. Here, the retainer comprises a sidewall provided with the counter threaded section to engage with the threaded section as provided on the barrel sidewall of the barrel of the medicament container. Here, the proximal fastening structure may be void of a barrel flange. In some examples the threaded section of the proximal fastening structure is an outer threaded section. It may be provided on an outside facing surface of the barrel sidewall. Complementary, the counter threaded section may comprise an inner threaded section or an inner thread. It may be provided on an inside surface of a sidewall of the retainer.

[0089] According to another example the threaded section is an inner threaded section. It may be provided on an inside surface of the barrel sidewall. Correspondingly, the counter threaded section may be implemented as an outer threaded section. It may be provided on an outside surface of the sidewall of the retainer.

[0090] By way of a threaded engagement between the retainer and the proximal fastening structure there can be provided a longitudinal or axial clamping of the sealing member engaged with at least one of the barrel sidewall and the sidewall or bottom of the retainer.

[0091] According to a further example the sealing member comprises an O-ring arranged or fixed inside the retainer. It may be configured to sealingly engage with the proximal end of the barrel. The O-ring may be provided at a longitudinal end of a sidewall of the retainer. Alternatively, the O-ring may be provided on or at the proximal end of the barrel sidewall.

[0092] In some examples the O-ring may be compressed or squeezed upon a threaded engagement between the retainer and the proximal fastening structure. In this way there can be provided a comparatively good, and durable hermetic seal between the retainer and the proximal fastening structure.

[0093] According to a further example the barrel comprises a radially outwardly extending funnel portion towards the proximal end of the barrel. Here, at least an inside surface of the barrel sidewall may radially widen towards the proximal end. At least an inside of the barrel sidewall may comprise a tapered structure with an increasing diameter towards the proximal end.

[0094] In some examples the barrel may be of substantially cylindrical or tubular shape. It may be only a proximal end section of the barrel sidewall that widens into a funnel portion.

[0095] A radially widening or conically-shaped funnel portion at the proximal end of the barrel may provide an improved sealing effect with a complementary shaped sealing member.

[0096] According to a further example the sealing member comprises an insert portion, e.g. in form of a kind of a sealing stopper. The insert portion of the sealing member comprises a tapered sidewall section to engage with a funnel portion of the barrel. The taper angle of the sidewall of the insert portion of the sealing member may correspond to a respective taper angle of the final portion of the barrel sidewall of the barrel at the proximal end of the barrel. In this way, there can be provided an improved sealing effect when the sealing member with its tapered or beveled sidewall section gets in direct contact with an inside surface of the funnel portion of the barrel.

[0097] By way of a radially widening funnel portion complementary shaped to a tapered sidewall section of the insert portion of the sealing member there can be provided an improved mutual sealing effect, e.g., on the basis of an increased mutual sealing or abutment surface.

[0098] At the same time the funnel shape and the tapered sidewall section may firmly engage due to their corresponding geometries and may form a kind of a press fit, which is configured to exhibit excellent sealing capabilities.

[0099] In another aspect the present disclosure also relates to an injection device. The injection device comprises a medicament container as described above. Insofar all features, effects and benefits as described above in connection with the medicament container equally apply to the injection device. In addition to the medicament container the injection device comprises a plunger. The plunger is configured to connect or to cooperate with the stopper located inside the barrel of the medicament container. The plunger is configured to displace the stopper in distal direction relative to the barrel for expelling of the medicament through the outlet.

[0100] The plunger may be provided as a separate piece. It may be initially disconnected from the plunger. Engagement or cooperation between the plunger and the stopper may require detachment and / or disintegration of the hermetic closure at the proximal end of the barrel. Removal of the hermetic closure or disintegrating of the hermetic closure may be required for inserting the plunger into the interior of the barrel from the proximal end of the barrel such that the plunger mechanically engages the stopper.

[0101] The plunger may be engaged with the stopper immediately before administering of the medicament through the outlet of the barrel. During transportation and storage, in particular during cryopreservation or storage of the medicament container at ultralow temperatures the plunger is effectively useless. It may be stored and provided as a separate piece in addition to the medicament container.

[0102] Upon inserting the plunger into the proximal end of the barrel the medicament container may transition into the injection device, which is then directly usable to inject or to expel the medicament through the distally located outlet of the barrel.

[0103] According to a further example the medicament container contains a medicament. The medicament may comprise a liquid medicament. The medicament may comprise an injectable medicament. The medicament may be stored or contained inside the interior of the barrel. It may be located between the stopper and the outlet of the barrel of the medicament container. This way and by pushing the stopper in distal direction the medicament can be expelled through the outlet.

[0104] According to a further example of the injection device the outlet of the medicament container comprises an injection needle or is provided with an injection needle. The injection needle may be non-detachably fixed to the outlet of the medicament container. It may extend through a sidewall or front wall of the medicament container. In some examples the medicament container terminates in a nozzle towards the distal direction. Here, the injection needle may protrude or may extend through the nozzle or through a tapered section at the distal end of the barrel. The injection needle may be initially covered by a protective cap, e.g. by a needle cap.

[0105] In other examples the outlet of the medicament container of the injection device is provided with a connector for at least one of a needle and an infusion line. The connector may be implemented as one of a male or female Luer connector providing a standardized fluid transferring connection with at least one of an injection needle and an infusion line provided or equipped with a complementary shaped female or male Luer connector.

[0106] According to another example of the injection device the injection device is implemented and / or configured as a pre-filled syringe. The pre-filled syringe is suitable for a direct injection of the medicament through the outlet, e.g. through an injection needle provided or extending through the outlet of the barrel of the medicament container.

[0107] Moreover, and due to the hermetic closure at the proximal end of the barrel the pre-filled syringe is likewise suitable for long-term storage and / or for storage at comparatively low temperatures. In effect, the pre-filled syringe is suitable for cryopreservation of the medicament located therein.

[0108] According to a further aspect the present disclosure also relates to a method of storing or preserving of a medicament in a medicament container at ultralow temperatures or cryogenic temperatures. In some examples the method is dedicated to a method of cold storage and / or cryopreservation of a medicament in a medicament container as described above. Insofar, all features, effects and benefits as described above in connection with the medicament container and as described above with the injection device may equally apply to the method of cryopreservation.

[0109] The method is particularly characterized by numerous method steps. In a first step there is provided a barrel of the medicament container. The barrel comprises a barrel sidewall, which defines a longitudinal direction and which comprises a distal end and a proximal end. As described above the proximal end of the barrel is located opposite the distal end. The proximal end and the distal end may form longitudinal opposite ends of the elongated barrel.

[0110] The barrel further comprises an outlet at the distal end. In a further method step, there is inserted a stopper into the barrel and the barrel is sealed towards the proximal end by the stopper. The stopper may be compressed while or during insertion into the barrel to form a liquid tight seal with an inside surface of the barrel sidewall. At the same time the stopper is still movable relative to the barrel when exerting a respective displacement force, which is larger than a friction force as applied by the stopper to an inside surface of the barrel sidewall.

[0111] Before or after insertion of the stopper into the barrel there is introduced a medicament into an interior of the barrel. In some examples the medicament is introduced into the barrel between the stopper and the outlet under aseptic conditions.

[0112] In some examples the stopper is introduced into the barrel after the medicament has been filled into the barrel. Typically, filling of the medicament into the barrel is conducted under aseptic conditions. Also, with some examples, the medicament may be filled into the barrel after insertion of the stopper into the barrel. Here, the medicament may be filled into the filling volume of the barrel, which is confined in longitudinal direction by the outlet and by the stopper, by piercing or penetrating through at least one of the outlet and the stopper with a filing device, such as a tipped filling needle.

[0113] Filling of the barrel and hence the interior of the barrel with the medicament under aseptic conditions provides a high quality and long-term storage of the medicament inside the barrel. As a further step the proximal end of the barrel is hermetically sealed by a hermetic closure, e.g. by a hermetic closure as described above.

[0114] A so-filled barrel is particularly suitable for long-term storage at comparatively low temperatures, e.g. at cryopreservation temperature, e.g. at or below -80°C, below -120°C or even below - 160°C. During a cooling of the medicament container the medicament, the barrel and / or the stopper may exhibit different thermal expansion or thermal contraction effects, which may cause a deformation and / or movement of the stopper relative to the barrel sidewall. Such a deformation or movement of the stopper relative to the barrel may be deficient to container closure integrity in the interface between the barrel sidewall and the stopper. However, by hermetically sealing the proximal end of the barrel by the hermetic closure a temporary deficiency in container closure integrity between the stopper and the barrel sidewall may not have any detrimental effect to the medicament.

[0115] Even though the stopper may temporarily exhibit insufficient container closure capabilities or insufficient sealing capabilities by way of the hermetic closure as provided at the proximal end of the medicament container, ingress of any contaminants from outside the container into the interior of the barrel can be effectively prevented.

[0116] Typically, the proximal end of the barrel is hermetically sealed by the hermetic closure while the medicament container is still under a septic conditions, which conditions are comparable to those aseptic conditions in which the medicament is filled or introduced into the interior of the barrel.

[0117] According to a further example the method of cryopreservation of the medicament further comprises the step of cooling the medicament container to a predefined cryopreservation temperature. During this cooling process and when reaching the final cooling temperature the hermetic closure at the proximal end of the barrel provides an hermetic seal by way of which any imperfections or disadvantages in the interface between the stopper and the barrel sidewall can be effectively balanced and / or compensated.

[0118] According to a further aspect the present disclosure also relates to a method of preparing a medicament for injection by making use of a medicament container, e.g., by making use of a medicament container as described above. The medicament container comprises a barrel with a barrel sidewall defining a longitudinal direction and comprising a distal end and a proximal end opposite the distal end. The barrel further comprises an outlet at the distal end. Inside the barrel there is provided a movable stopper, which is movable relative to the barrel in longitudinal direction. The stopper seals the barrel towards the proximal end. There is further contained a medicament in an interior of the barrel. The medicament is located inside the barrel longitudinally between the outlet and the movable stopper. A proximal end of the barrel is hermetically sealed by a hermetic closure.

[0119] Use of the medicament container now includes at least one of a detachment of the hermetic closure from the proximal end of the barrel or disintegration of the hermetic closure at the proximal end of the barrel and introducing a plunger into the interior of the barrel from the proximal end of the barrel. In an optional step the plunger is connected or engaged with the stopper, e.g. with a proximal side of the stopper. The medicament container may then transition into an injection device, which may be ready for injecting the medicament through the outlet by moving the plunger and the stopper in distal direction relative to the barrel sidewall of the medicament container.

[0120] Typically, the method of preparing the medicament may be conducted or implemented by making use of a medicament container and / or by an injection device as described above. Insofar, all features, effects and benefits as described above in connection with the medicament container may equally apply to the method of preparing the medicament container for injecting or expelling a medicament.

[0121] The disclosure also relates to a medicament container, an injection device and to a method as defined by the clauses and their mutual dependencies as given below.

[0122] Clause 1 : A medicament container (10) comprising: a barrel (11) with a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), an outlet (14) at the distal end (15), a stopper (20) located inside the barrel (11), sealing the barrel (11) towards the proximal end (16) and movable relative to the barrel (11) to expel a medicament (8) through the outlet (14), a proximal fastening structure (18) at the proximal end (16), and a hermetic closure (30) at the proximal end (16) to hermetically seal the proximal end (16).

[0123] Clause 2: The medicament container (10) according to clause 1 , wherein the hermetic closure (30) comprises a sealing member (32; 72) and a retainer (40; 50; 70), wherein the sealing member (32; 72) is configured to sealingly engage with the proximal end (16) of the barrel (11), and wherein the retainer (40; 50; 70) is configured to fix the sealing member (32) to the proximal end (16).

[0124] Clause 3: The medicament container (10) according to clause 2, wherein the retainer (40; 50; 70) comprises a cup-shaped cap portion (41 ; 71) comprising a sidewall (42; 73) and a bottom (43; 74) to at least partially enclose at least a portion of the sealing member (32; 72).

[0125] Clause 4: The medicament container (10) according to clause 2 or 3, wherein the retainer (40; 50; 70) comprises a counter fastening structure (45; 55; 75) complementary shaped to the proximal fastening structure (18).

[0126] Clause 5: The medicament container (10) according to clause 4, wherein the counter fastening structure (45; 75) of the retainer (40) is provided on or in the sidewall (42) of the cupshaped cap portion (41; 71).

[0127] Clause 6: The medicament container (10) according to any one of the preceding clauses 2 - 5, wherein the retainer (40) comprises a crimped cap (65) or crimpable cap (65) to positively engage with the proximal fastening structure (18).

[0128] Clause 7: The medicament container (10) according to clause 2 to 6, wherein the retainer (40) comprises a predetermined breaking structure (68) and a tear-off portion (69) to disintegrate the retainer (40).

[0129] Clause 8: The medicament container (10) according to clause 2 to 7, wherein at least a portion of the retainer (40) is covered by a cover (64). Clause 9: The medicament container (10) according to any one of the preceding clauses, wherein the proximal fastening structure (18) comprises a barrel flange (19) protruding radially outwardly from the sidewall (12) of the barrel (11).

[0130] Clause 10: The medicament container (10) according to clause 6, wherein the crimped cap (65) of the retainer (40) is positively engaged with the barrel flange (19).

[0131] Clause 11 : The medicament container (10) according to any one of the preceding clauses, wherein the sidewall (12) of the barrel (11) is of substantially tubular shape and transitions into a radially narrowing shoulder portion followed by a radially narrowed neck portion (5) towards the proximal end (16) of the barrel (11).

[0132] Clause 12. The medicament container (10) according to clause 9 or 10, wherein the retainer (50) comprises a first retainer part (51) and a second retainer part (52), wherein the first retainer part (51) and the second retainer part (52) each comprise a receptacle (53) sized and configured to receive at least a portion of the barrel flange (19) and a portion of the sealing member (32), which is in longitudinal abutment with the barrel flange (19).

[0133] Clause 13. The medicament container (10) according to clause 12, wherein the sealing member (32) comprises a flange portion (35) in longitudinal abutment with the barrel flange (19) and wherein the receptacles (53) of the first retainer part (51) and of the second retainer part (52) are each confined by a sidewall (54), a bottom portion (56) and an upper portion (57), wherein a size of an aperture of the receptacle (53) between the bottom portion (56) and the upper portion (57) is less than or equal to a combined longitudinal extent of the barrel flange (19) and the flange portion (35) of the sealing member (32).

[0134] Clause 14. The medicament container (10) according to clause 12 or 13, wherein the first retainer part (51) is engageable with a first barrel flange portion (19') of the barrel flange (19) and wherein the second retainer part (52) is engageable with a second barrel flange portion (19") of the barrel flange (19), which is circumferentially offset from the first barrel flange portion (19')

[0135] Clause 15: The medicament container (10) according to any one of the preceding clauses 12 to 14, further comprising a fixing element (60) with a first counter fastener (62') and a second counter fastener (62"), wherein the first retainer part (51) comprises a first fastener (58') to engage with the first counter fastener (62'), and wherein the second retainer part (52) comprises a second fastener (58") to engage with the second counter fastener (62").

[0136] Clause 16: The medicament container (10) according to clause 15, wherein the fixing element (60) comprises a fixing disc (61) and wherein first counter fastener (62') and the second counter fastener (62") each comprise an aperture (63) extending through the fixing disc (61).

[0137] Clause 17: The medicament container (10) according to clause 15 or 16, wherein the first fastener (58') and / or the second fastener (58") comprises a projection (59) configured for insertion into or through the aperture (63) of at least one of the first counter fastener (62') and the second counter fastener (62").

[0138] Clause 18: The medicament container (10) according to any one of the preceding clauses, wherein the outlet (14) comprises a nozzle (25) and a connector (26) for a needle (27).

[0139] Clause 19: The medicament container (10) according to any one of the preceding clauses, wherein the outlet (14) is provided with an injection needle (27) extending into an interior (13) of the barrel (11) of the medicament container (10).

[0140] Clause 20. The medicament container (10) according to any one of the preceding clauses 2 - 19, wherein the proximal fastening structure (18) comprises a threaded section (77) to engage with complementary shaped counter threaded section (76) of the retainer (70).

[0141] Clause 21 : The medicament container (10) according to clause 2 to 20, wherein the sealing member (72) comprises an O-ring inside the retainer (70) and configured to sealingly engage with the proximal end (16) of the barrel (11).

[0142] Clause 22: The medicament container (10) according to any one of the preceding clauses, wherein the barrel (11) comprises a radially outwardly extending funnel portion (6) towards the proximal end (16) of the barrel (11).

[0143] Clause 23: The medicament container (10) according to clause 2 and according to clause 22, wherein the sealing member (32) comprises an insert portion (33) with a tapered sidewall section (34) to engage with the funnel portion (60) of the barrel (11). Clause 24: An injection device (1) comprising a medicament container (10) according to any one of the preceding clauses and comprising a plunger (80) configured to connect and / or to engage with the stopper (20) and configured to displace the stopper (20) in distal direction relative to the barrel (11) for expelling of the medicament (8) through the outlet (14).

[0144] Clause 25: The injection device (1) according to clause 24, wherein the medicament container (10) contains a medicament (8).

[0145] Clause 26: The injection device (1) according to clause 25, wherein the outlet (14) of the medicament container (10) comprises an injection needle (27).

[0146] Clause 27: The injection device (1) according to any one of the clauses 24 to 26, wherein the injection device (1) comprises a pre-filled syringe (2).

[0147] Clause 28: An injection system comprising a medicament container (10) according to any one of the preceding clauses 1 - 23, wherein the proximal end (16) of the barrel (11) is void of a barrel flange (19), the injection system further comprising a separate flange part (90) comprising a sidewall portion (92) and a flange portion (91) protruding radially outwardly at a proximal end of the sidewall portion (92).

[0148] Clause 29: The injection system according to clause 28, wherein the sidewall portion (92) comprises a counter fastening structure (95) configured to engage with the proximal fastening structure (18) at the proximal end (16) of the barrel (11) of the medicament container (10).

[0149] Clause 30: A method of storing or preserving of a medicament (8) in a medicament container (10) at ultralow temperatures or cryogenic temperatures, the method comprising the steps of: providing of a barrel (11) of the medicament container (10), wherein the barrel (11) comprises a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), wherein the barrel (11) further comprises an outlet (14) at the distal end (15), inserting of a stopper (20) into the barrel (11) and sealing the barrel (11) towards the proximal end (16) by the stopper (20), introducing a medicament (8) into an interior (13) of the barrel (11) between the stopper (20) and the outlet (14) under aseptic conditions, hermetically sealing the proximal end (16) of the barrel (11) by a hermetic closure (30). Clause 31 : The method of clause 28 further comprising the step of cooling the medicament container (10) to a predefined cryopreservation temperature.

[0150] Clause 32 A method of storing or preserving a medicament (8) in a medicament container (10) at ultralow temperatures or cryogenic temperatures, the method comprising the steps of: providing of a barrel (11) of the medicament container (10), wherein the barrel (11) comprises a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), wherein the barrel (11) further comprises an outlet (14) at the distal end (15), introducing a medicament (8) into an interior (13) of the barrel (11) under aseptic conditions, inserting of a stopper (20) into the barrel (11) and sealing the barrel (11) towards the proximal end (16) by the stopper (20), hermetically sealing the proximal end (16) of the barrel (11) by a hermetic closure (30).

[0151] Generally, the scope of the present disclosure is defined by the content of the claims and / or clauses. The disclosure is not limited to specific embodiments or examples but comprises any combination of elements of different embodiments or examples. Insofar, the present disclosure covers any combination of claims and any technically feasible combination of the features disclosed in connection with different examples or embodiments.

[0152] The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0153] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0154] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

[0155] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0156] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

[0157] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0158] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0159] Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1 , ZYD-1, GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP- 2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA- 15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide- XTEN and Glucagon-Xten.

[0160] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom. Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0161] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0162] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0163] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0164] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0165] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0166] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

[0167] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0168] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0169] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container. As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0170] As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0171] Brief description of the drawings

[0172] In the following, some examples of a medicament container and an injection device for cooled storage of an injectable medicament will be described in greater detail by making reference to the drawings, in which:

[0173] Fig. 1 shows an example of a medicament container,

[0174] Fig. 2 shows an example of an injection device with another medicament container in an explosive illustration,

[0175] Fig. 3 shows a further example of the medicament container in a final assembly configuration,

[0176] Fig. 4 shows the medicament container according to Fig. 3 with the individual components of the hermetic closure cap

[0177] Fig. 5 is a perspective illustration of first and second retainer parts of a retainer of the hermetic closure,

[0178] Fig. 5a is a perspective illustration of a variant of a retainer parts according to Fig.5,

[0179] Fig. 6 is an exemplary implementation of a barrel flange as seen from the proximal end of the barrel, Fig. 7 shows a further example of a hermetic closure in a pre-assembly configuration,

[0180] Fig. 8 shows the example according to Fig. 7 in a final assembly configuration,

[0181] Fig. 9 is a perspective illustration of an example according to Figs. 7 and 8 prior to a detachment of the retainer,

[0182] Fig. 10 shows a further configuration of the retainer during detachment or disintegration,

[0183] Fig. 11 shows a further example of the medicament container,

[0184] Fig. 12 shows a further example of the medicament container,

[0185] Fig. 13 shows another example of the medicament container,

[0186] Fig. 14 shows a plunger and a flange part for separate assembly to the barrel as shown in

[0187] Fig. 13,

[0188] Fig. 15 is a flowchart of a method of cryopreservation of a medicament, and

[0189] Fig. 16 is a flowchart of a method of preparing a medicament with a medicament container as described herein.

[0190] Detailed Description

[0191] In Figs. 1 and 2 there is illustrated an example of an injection device 1. The injection device 1 comprises a medicament container 10 and further comprises a plunger 80. The plunger 80 may be provided separate to the medicament container 10. Hence, the medicament container 10 as shown in Fig. 1 and the plunger 80 may form an injection kit, which, when assembled may provide the injection device 1 , which is ready for injecting and / or expelling a medicament 8.

[0192] The medicament container 10 is particularly suitable for long-form storage of the medicament 8, particularly at comparatively low temperatures, such as ultra-low temperatures of cryopreservation temperatures, e.g. at or below -80°C, below -120°C or even below -160°C.

[0193] The medicament container may be further directly used as an injection device after termination of a cooling and / or cryopreservation process.

[0194] The medicament container 10 comprises an elongated barrel 11 with a barrel sidewall 12. The barrel 11 can be made of a vitreous material, e.g. class. In some examples, the barrel can be made of a plastic material. The barrel comprises a distal end 15 and an oppositely located proximal end 16. The distal end 15 is provided with an outlet 14. There, the barrel 11 or container 10 may be provided with a nozzle 25. The outlet 14 may be covered by a protective cap 28, which may be implemented as a needle cap. In the example of Fig. 2 the distal end 15 of the barrel 11 is provided with an injection needle 27, which may be covered by a needle cap 28. In the example of Fig. 1, the distal end 15 may be further provided with a connector 26, which may be complementary shaped to a respective counter connector for establishing a fluid transferring connection between the outlet 14 and the nozzle 25, e.g. with at least one of a needle 27 and an infusion line (not illustrated) that may be equipped with the respective counter connector. Towards the distal end 15 the tubularly-shaped sidewall 12 radially narrows into a shoulder portion 17, which merges in the nozzle 25.

[0195] The barrel 11 confines an interior 13, which is configured to receive and to contain the medicament 8, which may be provided as a liquid injectable medicament. In proximal direction, hence towards the proximal end 16 the barrel 11 is sealed by a stopper 20. The stopper 20 comprises a stopper body 21, which may be made of an elastic material, which is capable to effectively seal the inside or interior 13 of the barrel 11 towards the proximal end 16. The stopper 20 comprises a distal face 22 facing towards the medicament 8. The stopper 20 also comprises a proximal face 23 facing towards the proximal end 16. The stopper 20 may sealingly engage with an inside surface of the barrel sidewall 12. It may be slidably movable in longitudinal direction to expel the medicament 8 through the outlet 14. The proximal side 23 the stopper 20 may comprise a fastening structure 24 to engage with a complementary shaped counter fastening structure 84 as provided at a distal end of a plunger shaft 81 of the plunger 80 as shown in Fig. 2. The plunger 80 may further comprise a finger flange 82 at a proximal end of the plunger shaft 81.

[0196] Hence, the plunger 80 may be connected or connectable to the fastening structure 24 of the stopper 20. In such a configuration the medicament container 10 may transition into the injection device 1 and the plunger 80 can be used to displace or to urge the stopper 20 in distal direction and hence towards the outlet 14 for expelling of the medicament through the outlet 14.

[0197] A circumferential side wall of the stopper 20 or stopper body 21 may comprise one or numerous sealing lips or lamellae, by way of which a sealing effect with the inside surface of the barrel sidewall 12 can be improved.

[0198] However, and when subject to ultralow or cryopreservation temperatures the sealing capability of the stopper 20 with respect to the inside surface of the barrel sidewall 12 may become insufficient. For this the medicament container 10 is provided with a hermetic closure 30 at the proximal end 16 of the barrel 11. The hermetic closure 30 serves to hermetically seal the proximal end 16. The hermetic closure 30 is typically attached or engaged with the proximal end 16 and hence with a proximal fastening structure 18 of the barrel 11 as provided at the proximal end 16.

[0199] By way of the hermetic closure 30, the interior 13 of the barrel 11 can be effectively sealed against ingress of any contaminants. In this way and even if the container closure integrity of the sealing capability between the stopper 20 and the barrel sidewall 12 should become insufficient the hermetic closure 30 forms or constitutes a hermetic closure by way of which ingress of any contaminants or other harmful substances is effectively prevented.

[0200] In the example of Figs. 1 and 2, the hermetic closure 30 comprises a sealing member 32, e.g. of elastomeric or plastic material, which effectively seals the proximal end 16 of the barrel 11. The sealing member 32 is mechanically fastened to the proximal end 16 by way of a retainer 40.

[0201] The retainer 40 comprises a cup - shaped cap portion 41. The retainer 40 further comprises a sidewall 42, which is configured to engage the proximal fastening structure 18 of the barrel 11. Typically, the cap portion 41 forms or constitutes a receptacle that is sized to receive portions of the sealing member 32 and at least a portion or portions of the proximal fastening structure 18.

[0202] In the example as shown in Figs. 1 and 2 the sealing member 32 comprises an insert portion 33, which is sized for insertion into the interior of the tubularly-shaped barrel sidewall 12. The insert portion 33 comprises an outwardly facing sidewall 34, which is complementary shaped to an inside structure or inside surface of the barrel sidewall 12 at or near the proximal end 16. In addition, the sealing member 32 comprises a flange or a flange portion 35 protruding radially outwardly from a proximal end of the insert portion 33.

[0203] The proximal fastening structure 18 is also provided with a barrel flange 19 protruding radially outwardly from an outside surface of the barrel sidewall 12. The flange portion 35 of the sealing member 32 comprises a distally facing abutment face 36, which is shaped and configured to longitudinally abut a proximally facing abutment face of the barrel flange 19. Insofar and when inserting the sealing member 32 into the proximally open ended barrel 11 there can be provided a two-fold sealing effect, namely between an inside of the barrel sidewall 12 and an outside sidewall 34 of the sealing member 32. In addition, there can be provided a sealing effect between the distally facing abutment face 36 of the flange portion 35 of the sealing member 32.

[0204] An outer edge 39 of the flange portion 35 may be equal in size or slightly smaller than an outside edge of the barrel flange 19. In in this way, the barrel flange 19 as well as the outer edge 39 of the end portion 35 can be received in the receptacle as formed by the bottom 43 and the sidewall 42 of the retainer 40. A distal end of the sidewall 42 of the retainer 40 is provided with a counter fastening structure 44, which is complementary shaped to the proximal fastening structure 18 of the barrel 11. In this way and as shown in Fig. 1 the counter fastening structure 44 engaging with the proximal fastening structure 18 serves to provide a permanent fastening and fixing of the sealing member 32 to the proximal end 16 of the barrel 11. The bottom 43 confines the receptacle in proximal direction and may engage with the flange portion 35 and / or with a proximal side of the sealing member 32. Hence, in the illustration according to Figs. 1 into the receptacle confined by the bottom 43 and the sidewall 42 is in a kind of an upside down configuration with an insert opening facing in distal direction 2.

[0205] It may be even provided that the sealing member 32 is held or fixed in a longitudinally or axially compressed configuration when the proximal fastening structure 18 engages the counter fastening structure 44 of the retainer 40. As indicated in Figs. 1 and 2 the bottom 43 of the retainer 40 may abut with a proximal abutment face 38 of the sealing member 32. At the same time the sidewall 42 may extend longitudinally across the outer edge 39 and the barrel flange 19 and grips under a recessed section at a distal side of the barrel flange 19 by way of snap elements 45 that are provided at the distal end of the sidewall 42. There may be provided numerous snap elements 45 by way of which there can be provided a snap-type fastening when pushing the container 40 in distal direction onto the assembly of barrel flange 19 and sealing member 32.

[0206] As illustrated in Fig. 2 the snap element 45 may be even provided with a beveled edge 46 by way of which there may be induced a radially outwardly directed bending or deformation of the sidewall 42 or sections thereof during a final step of assembly, namely when the retainer 40 is pushed onto the sealing member 32 and barrel flange 19 in distal direction.

[0207] As further illustrated in Fig. 2 the sidewall 42 and / or the snap element 45 may be provided with a gripping element 48. The gripping element 48 may protrude radially outwardly from the sidewall 42 and may support an elastic deformation or disintegration of the counter fastening structure 44. Here, a user may easily grip the radially outwardly protruding gripping element 48 and may apply a dedicated force onto the gripping element 48, which may be integrally formed or integrated into the sidewall 42. This way, a user may easily induce a deformation of the sidewall 42 and hence of the counter fastening structure 44 thereby enabling a rather easy disconnection of the counter fastening structure 44 from the proximal fastening structure 18.

[0208] However, and when reaching the final assembly configuration, in which the snap element 45 has passed the outer and distal edge of the barrel flange 19 the snap element 45 may relax radially inwardly thereby engaging the distal side of the barrel flange 19 and thereby holding and fixing the sealing member 32 to the barrel flange 19 with regard to the longitudinal direction.

[0209] The sealing member 32 is firmly held at the proximal end 16 of the barrel 11 to such an extent that the hermetic closure 30 hermetically seals the proximal end 16 of the barrel 11 even at ultralow or cryopreservation temperatures.

[0210] The hermetic closure 30 may be detachably connectable to the proximal end 16 of the barrel 11. Detachment of the hermetic closure 30 may be intended or maybe even necessary immediate before preparation of the medicament 8 for injection or expelling of the medicament 8. For detaching the hermetic closure 30 from the proximal end 16 of the barrel 11 it may be required that the retainer 40 is either disintegrated or destroyed or that the counter fastening structure 44 and hence the snap element 45 is transferred into a release configuration, in which the retainer 40 can be detached from the barrel flange 19. Subsequently or concurrently with a detachment of the retainer 40 also the sealing member 32 can be detached from the proximal end 16 thus providing access to the proximal side 23 of the stopper 20, which may then engaged with the distal end of the plunger 80 or plunger rod 81 for conducting medicament dispensing or medicament injection through the outlet 14.

[0211] In Figs. 7-12 there are illustrated further examples of a hermetic closure 30, that can be likewise used with a barrel 11 provided with a barrel flange 19, which provides or constitutes the proximal fastening structure 18.

[0212] In the example of Fig. 7-10 there may be used a likewise sealing member 32, that is configured and sized for insertion into the proximally open end of the barrel 11. The retainer 40 is slightly modified compared to the retainer 40 as described in connection with Figs. 1 and 2. Here, the retainer 40 also comprises a cup - shaped cap portion 41 with a bottom 43 and a sidewall 42. However, the retainer 40 is implemented as a crimped cap 65 or crimped cup, which is plastically deformable after engagement with the sealing member 32 and the barrel flange 19. In some examples the retainer 40 is made of a sheet metal, such as aluminum, which is easily plastically deformable.

[0213] In the example of Fig. 7 the retainer 40 is already shown in the crimped and hence in the end configuration. In an initial configuration the sidewall 42 is of somewhat tubular shape. It comprises a distal end that is sized to slip or to slide over the preassembly of the barrel flange 19 and the sealing member 32. It may be then and during final assembly that the distal end of the sidewall 42, which is opposite the bottom 43, is crimped radially inwardly and is hence plastically deformed, e.g. by making use of a respective crimping tool.

[0214] It is then that a distal end of the sidewall 42 is bended or plastically deformed radially inwardly so as to form a crimped section 66 that grips under the radially outwardly extending barrel flange 19 as illustrated in Fig. 8. The crimped cap 65 and hence the retainer 40 may be made of a plastically deformable material, such as aluminum or the like plastically deformable material. During or before a crimping process the retainer 40 and hence the crimped cap 65 may be press fitted together with the sealing member 32 to the proximal end 16 so as to provide a sufficient sealing and fixing of the sealing member 32 to the proximal end 16 of the barrel sidewall 12.

[0215] An outside surface of the bottom 43 of the crimped cap 65 may be provided with a lining or cover 64. The cover 64 may provide a supplemental environmental protection for the bottom 43 of the retainer 40. In some examples and as illustrated in Figs. 9 and 10 the crimped cap 65 may be provided with a predetermined breaking structure 68 and with a tear-off portion 69. The tear-off portion 69 may be actuatable or grippable by a user in order to tear away or to disintegrate the crimped cap 65.

[0216] Hence, there may be provided an integrated gripping portion 67, e.g. in form of an eyelet that is easily and intuitively grippable by a user to pull away the tear-off 69 by way of which the crimped cap 65 disintegrates along the predetermined breaking structure 68. The predetermined breaking structure 68 may extend from the bottom 43 into and through the entirety of the sidewall 42. This may allow to rupture the entire sidewall 42 in order to enable a detachment of the crimped cap 65 from the proximal end 16 of the barrel 11. The cover 64 may comprise a plastic sheet or plastic foil to prevent inadvertent gripping or inadvertent or unauthorized actuation of the tear-off portion 69.

[0217] In Fig. 11 there is illustrated another example of a medicament container 10. Here, the medicament container 10 may be provided with a hermetic closure 30 as described before. Here, the proximal end 16 of the barrel 11 is provided with a radially narrowed neck portion 5. The tubularly-shaped barrel sidewall 12 transitions in proximal direction and hence towards the proximal end 16 via a radially narrowing shoulder portion 4 into the radially narrowed neck portion 5. The narrowing shoulder portion 4 and the neck portion 5 are provided at least on the outside of the barrel 11. The inside structure or inside surface of the barrel may remain completely or at least partially unaffected by the modified outside surface structure of the barrel 11 at or near its proximal end 16.

[0218] The radially narrowed neck portion 5 provides an increased radial recess at the distal side of the barrel flange 19, which may improve or facilitate a crimping or otherwise form-fitting engagement between the retainer 40 and the proximal fastening structure 18. It may be also provided that in the region of the radially narrowed neck portion 5 the inner diameter of the barrel 11 is reduced compared to a diameter or radial cross section as provided in the distal or middle longitudinal section of the cylindrical portion of the barrel sidewall 12. This may even help to detach a plunger 80 after use from the injection device 1 and when withdrawing the plunger 80 and the stopper 22 towards the proximal end 16. Here and with the radially narrowed through opening as provided at the proximal end 16 of the barrel 11 the stopper 20 cannot be removed from the barrel 11. Rather, a friction fit or the like mechanical connection between the fastening structure 24 at the proximal side 23 of the stopper 20 and the complementary shaped counter fastening structure 84 as provided at the distal end of the plunger shaft 81 one can be easily abrogated by applying a sufficiently high pull-off force.

[0219] In the further example as shown in Fig. 12 the proximal end 16 of the barrel 11 is provided with a radially widening funnel portion 6 at or towards the proximal end 16. The funnel portion 6 comprises a tapered sidewall structure towards or near the proximal end 16 of the barrel 11. The funnel portion 6 may transition towards the proximal end 16 into the radially outwardly protruding barrel flange 19.

[0220] Here, the sealing member 32 is complementary shaped to the funnel portion 6. The sealing member 32 may be provided with an insert portion 33 featuring a beveled or tapered sidewall 34, which is complementary shaped to the shape of the funnel portion 6. A tapered structure of the sealing member 32 and the tapered of the funnel portion 6 may provide an improved sealing capability between the mutually engaging surfaces of the funnel portion 6 and the sidewall 34.

[0221] The retainer 40 according to Fig. 12 is identical to the retainer 40 described above in connection with Fig. 2. However, there may be used any kind of alternative retainer 40 as described herein that is suitable for or compatible with a barrel flange 19.

[0222] In the further example of Figs. 3-6 there may be used a sealing member 32 as described before in connection with any of Figs. 1, 2, or 9-11. But here, the retainer 50 comprises a first retainer part 51 and a second retainer part 52 which are separately illustrated in Fig. 5. Here, the first and the second retainer parts 51, 52 may be implemented identically. Each one of the retainer parts 51 , 52 comprises a receptacle 53, which is sized to receive at least a portion of the barrel flange 19 and the flange portion 35 of the sealing member 32 when engaged with the barrel flange 19. The receptacle 63 is sized and configured for mounting onto the radially outwardly protruding arrangement of the barrel flange 19 and the flange portion 35.

[0223] The receptacle 53 is delimited or confined in longitudinal direction by a bottom portion 56 and an upper portion 57. A longitudinal distance between the bottom portion 56 and the upper portion 57 is less than or equal than a combined longitudinal extent of the barrel flange 19 and the flange portion 35 of the sealing member 32. In this way, the receptacle 53 may form or constitute a counter fastening structure 55 of the first and second retainer part 51 , 52, respectively, which is configured to frictionally engage with the flange portion 35 and the proximal fastening structure 18.

[0224] In the present context it should be noted that the expressions of a bottom portion 56 and an upper portion 57 only define oppositely located confining structures of the receptacle 53, which delimit or confine the receptacle 53 in longitudinal or axial direction. In view of the cup-shaped geometry of the retainers 40, 50 and specifically in view of the first and second retainer part 51, 52 the bottom portion a portion of them first and second retainer part 51, 52 that confines the receptacle 53 in distal direction 2. The upper portion 57 confines the receptacle 53 in the opposite distal direction 3.

[0225] The upper portion 57 and the bottom portion 56 may extend substantially parallel to each other. They may comprise a planar shape extending in radial and circumferential direction with regard to the cylindrical shape of the barrel 11 of the medicament container 10.

[0226] In some examples the radial extent of the bottom portion 56 may be larger than the radial extent of the upper portion 57. In further examples, the radial extent of the bottom portion 56 may be substantially equal to the radial extent of the upper portion 57. In other examples the radial extent of the button portion 56 may be smaller than the radial extent of the upper portion 57.

[0227] In this way the first and second retainer parts 51 , 52 can be pushed radially inwardly onto the preassembly of the sealing member 32 in engagement with the barrel flange 19 to keep the flange portion 35 and hence the sealing member 32 in firm or longitudinally compressed engagement with the barrel flange 19.

[0228] As it is particularly illustrated in Fig. 4 and in the further example according to Fig. 5a the upper portion 57 comprises a radial extent that is at least in sections larger than the radial extent of the bottom portion 56. Moreover, and as shown in Fig. 5a the bottom portion 57 may comprise a radially recessed structure 49 adjoining an insert opening of the receptacle 53, which is complementary shaped to an outside circumference of the barrel 11 of the medicament container 10. In this way, and when receiving the flange portion 35 of the barrel flange 19 the radially recessed structure 49 of the bottom portion 57 may get in direct radial abutment with an outside surface of the barrel 11. Due to the recessed structure 49 there can be provided a comparatively large radial displacement of the first and second retainer part 51, 52 relative to the barrel 11 by way of which there can be provided a firm engagement between the barrel flange 19, the flange portion 35 and the receptacle 53.

[0229] As particularly illustrated in Fig. 6 the barrel flange 19 comprises a first flange portion 19' and a second flange portion 19". First and second flange portions 19', 19" protrude diametrically opposite from the outside surface of the tubularly-shaped sidewall 12 of the barrel 11.

[0230] According to further examples (not illustrated) the barrel flange 19 may be of annular shape. It may comprise a continuous or equal radial extent as seen in circumferential direction.

[0231] According to further examples the barrel flange 19 may be of rectangular or open shape. Generally, the geometry of the barrel flange 19 answers or of a radially outwardly extending collar is complementary shaped to a receptacle 53 of the first and second retainer parts 51, 52.

[0232] In further examples, the proximal fastening structure 18 may be provided with a collar extending radially outwardly from the sidewall 12 of the barrel 11 thus providing a form fitting engagement with the extending collar, which likewise provide or constitute a proximal fastening structure 18 to engage with the counter fastening structure 45, 55 of the retainer 40, 50.

[0233] The first and second retainer parts 51 , 52 each comprise a first and a second fastener 58', 58", implemented as a longitudinally extending projection 59 that protrudes from an outside surface of the upper portion 57. These fasteners 58', 58" may engage with respective counter fasteners 62', 62" of a fixing element 60 that is to be assembled to the retainer parts 51 , 52 after reaching a final assembly configuration as shown in Fig. 3.

[0234] It may be only upon reaching a final and radially innermost assembly configuration of the first and second retainer parts 51 , 52 that the respective first and second fasteners 58', 58" reach a distance or a configuration that matches with the configuration or distance between the respective counter fastener 62', 62". It may be only then that the fixing element 60, e.g. implemented as a planar fixing disc 61 , longitudinally engages with the projections 59.

[0235] Once the fixing element 60 with its counter fasteners 62', 62" is duly engaged with the fasteners 59 of the first and the second retainer parts 51 , 52 the first and second retainer parts 51 , 52 are mutually fixed with regards to the radial direction. They are longitudinally fixed to the proximal fastening structure 18 by or through firmly receiving the barrel flange 19 and the flange portion 35 of the sealing member 32.

[0236] In a further example as shown in Figs. 13 and 14 the proximal fastening structure 18 is void of a barrel flange 19. Here, the proximal end 16 of the barrel 11 is provided with an alternative proximal fastening structure 18. The proximal fastening structure 18 is provided with a threaded section 77 either on the outside or inside surface of the barrel sidewall 12. Here, the retainer 70 is provided with a complementary shaped counter threaded section 76 of a complementary shaped counter fastening structure 75. Here, the retainer 70 comprises a cup - shaped cap portion 71 with a bottom 74 and with a tubularly-shaped or cylindrically-shaped sidewall 73.

[0237] The counter fastening structure 75 and hence the counter threaded section 76 is provided on an inside or outside surface of the sidewall 73. In the illustration of Fig. 13 the counter threaded section 76 is implemented as an inner threaded section. The threaded section 77 is implemented as an outer threaded section. In other examples the inner and outer threaded sections may be provided in a opposite sense. Here, it may be the proximal fastening structure 18 that is provided with an inner threaded section and it may be the counter fastening structure 75 that is provided with an outer threaded section.

[0238] The retainer 70 may be equipped with a sealing member 72, which may be provided in form of an O-ring. Alternatively, an inside surface of the bottom 74 may be implemented as a sealing member and / or may be provided with a sealing disc, which engages the proximal end face of the barrel sidewall 12 upon establishing a screw connection between the retainer 70 and the proximal fastening structure 18.

[0239] The retainer 70 and hence the cap portion 71 may be intended and provided for storage and sealing at ultralow temperatures, e.g. for cryopreservation. For use of the medicament it is intended to detach the retainer 70 and / or the sealing member 72 simply by unscrewing the cap portion 71 from the proximal end 16 of the barrel 11. There may be then provided a separate flange part 90 comprising a sidewall portion 92 and a flange portion 91 protruding radially outwardly at a proximal end of the sidewall portion 92.

[0240] The sidewall portion 92 may comprise a surface, e.g. an inside surface 93 provided with a counter fastening structure 95 and hence with a counter threaded section 96 that resembles or that is substantially identical to the counter fastening structure 75 and to the counter threaded section 76 of the cap portion 71 of retainer 70. Hence, by way of the counter fastening structure 95 the flange part 90 can be likewise attached to the proximal fastening structure 18 instead of the retainer 70. The flange part 90 and hence its sidewall portion 92 comprises a longitudinal through opening 94 or through bore, which is sized to receive the plunger shaft 81 there through. In this way the medicament container 10 as shown in Fig. 13, which is initially void of a barrel flange 19, can be provided with a separate barrel flange of flange portion 91 by attaching the flange part 90 to the proximal end 16 after detaching the retainer 70 and the sealing member 72.

[0241] The flange part 90 may be readily provided with a plunger 80. The plunger 80 may be connected or engaged with the flange part 90. The flange part 90 as shown in Fig. 14 and the medicament container 10 as illustrated in Fig. 13 may form or constitute an injection system.

[0242] It should be noted that any of the sealing members 32 as described herein can be used with any of the retainers 40 as described herein even though a specific combination of sealing member 32 and retainer 40, 50, 70 may not be explicitly shown in detail.

[0243] Moreover, the retainer 50 as described in connection with Figs. 3-6 can be used with any of the sealing members 32 as described herein and with any proximal fastening structure 18 that is provided with a barrel flange 19.

[0244] The flowchart according to Fig. 15 is illustrative of a method of cryopreservation of a medicament 8 in a medicament container 10. Here and in a first 100 there is provided a barrel 11 of the medicament container 10. In a further step 102 a stopper 20 is inserted into the barrel 11 in order to seal the barrel 11 towards the proximal end 16. In step 104 there is introduced a medicament 8 into the interior 13 of the barrel 11 between the stopper 20 and the outlet 14 under aseptic conditions. Then and still under aseptic conditions and in step 106 the proximal end 16 of the barrel 11 is hermetically sealed by the hermetic closure 30 as described herein.

[0245] As a further optional step the medicament container 10 may be cooled down to a predefined cryopreservation temperature. Then, any shortcomings of a sealing capability of the stopper 20 that might be due to the variation or reduction in temperature may be compensated by the hermetic closure 30.

[0246] In the further flowchart of Fig. 16 there is illustrated a method of preparing a medicament as provided in a medicament container 10 as described herein. Here, and in a first step 200 the medicament container containing the medicament 8 and being sealed at its proximal end 16 with a hermetic closure 30 is provided. In step 202 the hermetic closure 30 at the proximal end 16 is either detached or is destroyed or disintegrated. In a subsequent step 204 a plunger 80 is inserted into the barrel 11 through the proximal end 16 of the barrel 11, and in step 206 the plunger 80 may be engaged or may get in abutment with the stopper 20 to form or to constitute an injection device 1, which is ready to use for conducting an injection or medicament expelling procedure.

[0247] Reference Numbers

[0248] 1 injection device

[0249] 2 syringe

[0250] 4 shoulder portion

[0251] 5 neck portion

[0252] 6 funnel portion

[0253] 7 inside surface

[0254] 8 medicament

[0255] 10 medicament container

[0256] 11 barrel

[0257] 12 sidewall

[0258] 13 interior

[0259] 14 outlet

[0260] 15 distal end

[0261] 16 proximal end

[0262] 17 shoulder portion

[0263] 18 proximal fastening structure

[0264] 19 barrel flange

[0265] 20 stopper

[0266] 21 stopper body

[0267] 22 distal face

[0268] 23 proximal face

[0269] 24 fastening structure

[0270] 25 nozzle

[0271] 26 connector

[0272] 27 needle

[0273] 28 protective cap

[0274] 30 closure

[0275] 32 sealing member

[0276] 33 insert portion

[0277] 34 sidewall

[0278] 35 flange portion

[0279] 36 abutment face

[0280] 38 abutment face

[0281] 39 outer edge

[0282] 40 retainer 41 cap portion

[0283] 42 sidewall

[0284] 43 bottom

[0285] 44 counter fastening structure

[0286] 45 snap element

[0287] 46 beveled edge

[0288] 47 projection

[0289] 48 gripping element

[0290] 49 recessed structure

[0291] 50 retainer

[0292] 51 retainer part

[0293] 52 retainer part

[0294] 53 receptacle

[0295] 54 sidewall

[0296] 55 counter fastening structure

[0297] 56 bottom portion

[0298] 57 upper portion

[0299] 58 fastener

[0300] 59 projection

[0301] 60 fixing element

[0302] 61 fixing disc

[0303] 62 counter fastener

[0304] 63 aperture

[0305] 64 cover

[0306] 65 crimped cap

[0307] 66 crimped section

[0308] 67 gripping portion

[0309] 68 predetermined breaking structure

[0310] 69 tear-off portion

[0311] 70 retainer

[0312] 71 cap portion

[0313] 72 sealing member

[0314] 73 sidewall

[0315] 74 bottom

[0316] 75 counter fastening structure

[0317] 76 counter threaded section

[0318] 77 threaded section 80 plunger

[0319] 81 plunger shaft

[0320] 82 finger flange

[0321] 84 counter fastening structure 90 flange part

[0322] 91 flange portion

[0323] 92 sidewall portion

[0324] 93 inside surface

[0325] 94 through opening 95 counter fastening structure

[0326] 96 counter threaded section

Claims

Claims1 . A medicament container (10) comprising: a barrel (11) with a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), an outlet (14) at the distal end (15), a stopper (20) located inside the barrel (11), sealing the barrel (11) towards the proximal end (16) and movable relative to the barrel (11) to expel a medicament (8) through the outlet (14), a proximal fastening structure (18) at the proximal end (16), and a hermetic closure (30) at the proximal end (16) to hermetically seal the proximal end (16).

2. The medicament container (10) according to claim 1 , wherein the hermetic closure (30) comprises a sealing member (32; 72) and a retainer (40; 50; 70), wherein the sealing member (32; 72) is configured to sealingly engage with the proximal end (16) of the barrel (11), and wherein the retainer (40; 50; 70) is configured to fix the sealing member (32) to the proximal end (16).

3. The medicament container (10) according to claim 2, wherein the sealing member (32) comprises a sealing stopper to engage with an inside surface of a sidewall (12) of the barrel (11). <pg. 6; Ins. 29 - 30>4. The medicament container (10) according to claim 2 or 3, wherein the retainer (40; 50; 70) comprises a cup-shaped cap portion (41 ; 71) comprising a sidewall (42; 73) and a bottom (43; 74) to at least partially enclose at least a portion of the sealing member (32; 72).

5. The medicament container (10) according to any one of the preceding claims 2 - 4, wherein the retainer (40; 50; 70) comprises a counter fastening structure (45; 55; 75) complementary shaped to the proximal fastening structure (18).

6. The medicament container (10) according to any one of the preceding claims 2 - 5, wherein the retainer (40) comprises a crimped cap (65) or crimpable cap (65) to positively engage with the proximal fastening structure (18).

7. The medicament container (10) according to claim 6, wherein the retainer (40) comprises a predetermined breaking structure (68) and a tear-off portion (69) to disintegrate the retainer (40).

8. The medicament container (10) according to any one of the preceding claims, wherein the proximal fastening structure (18) comprises one of a barrel flange (19) and a collar protruding radially outwardly from the sidewall (12) of the barrel (11).

9. The medicament container (10) according to claim 8, wherein the sidewall (12) of the barrel (11) is of substantially tubular shape and transitions into a radially narrowing shoulder portion (4) followed by a radially narrowed neck portion (5) towards the proximal end (16) of the barrel (11).

10. The medicament container (10) according to claim 8 or 9, wherein the retainer (50) comprises a first retainer part (51) and a second retainer part (52), wherein the first retainer part (51) and the second retainer part (52) each comprise a receptacle (53) sized and configured to receive at least a portion of the barrel flange (19) and a portion of the sealing member (32), which is in longitudinal abutment with the barrel flange (19).

11. The medicament container (10) according to claim 10, wherein the sealing member (32) comprises a flange portion (35) in longitudinal abutment with the barrel flange (19) and wherein the receptacles (53) of the first retainer part (51) and of the second retainer part (52) are each confined by a sidewall (54), a bottom portion (56) and an upper portion (57), wherein a size of an aperture of the receptacle (53) between the bottom portion (56) and the upper portion (57) is less than or equal to a combined longitudinal extent of the barrel flange (19) and the flange portion (35) of the sealing member (32).

12. The medicament container (10) according to any one of the preceding claims 10 or 11 , further comprising a fixing element (60) with a first counter fastener (62') and a second counter fastener (62"), wherein the first retainer part (51) comprises a first fastener (58') to engage with the first counter fastener (62'), and wherein the second retainer part (52) comprises a second fastener (58") to engage with the second counter fastener (62").

13. The medicament container (10) according to any one of the preceding claims 2 - 12, wherein the proximal fastening structure (18) comprises a threaded section (77) to engage with complementary shaped counter threaded section (76) of the retainer (70).

14. The medicament container (10) according to any one of the preceding claims, wherein the barrel (11) comprises a radially outwardly extending funnel portion (6) towards the proximal end (16) of the barrel (11).

15. The medicament container (10) according to claim 2 or 3 and according to claim 14, wherein the sealing member (32) comprises an insert portion (33) with a tapered sidewall section (34) to engage with the funnel portion (60) of the barrel (11). <pg. 17; Ins. 34 - 36>16. An injection device (1) comprising a medicament container (10) according to any one of the preceding claims and comprising a plunger (80) configured to connect and / or to engage with the stopper (20) and configured to displace the stopper (20) in distal direction relative to the barrel (11) for expelling of the medicament (8) through the outlet (14).

17. A method of storing or preserving of a medicament (8) in a medicament container (10) at ultralow temperatures or cryogenic temperatures, the method comprising the steps of: providing of a barrel (11) of the medicament container (10), wherein the barrel (11) comprises a barrel sidewall (12) defining a longitudinal direction and comprising a distal end (15) and a proximal end (16) opposite the distal end (15), wherein the barrel (11) further comprises an outlet (14) at the distal end (15), inserting of a stopper (20) into the barrel (11) and sealing the barrel (11) towards the proximal end (16) by the stopper (20), introducing a medicament (8) into an interior (13) of the barrel (11) between the stopper (20) and the outlet (14) under a aseptic conditions, hermetically sealing the proximal end (16) of the barrel (11) by a hermetic closure (30).

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