Medicament container, injection device and method of filling the same

Abstract

In one aspect the present disclosure relates to a method of providing an aseptic medicament container (10) for filling with a medicament (5), the method comprising: - providing a barrel (11) with a barrel sidewall (12) and comprising an outlet (14) at a distal longitudinal end (15) of the barrel (11), - inserting a stopper (20) into the barrel (11) from a longitudinal proximal end (16) of the barrel (11) and positioning the stopper (20) at a predefined longitudinal distance from the outlet (14) of the barrel (11) to confine an interior (13) of the barrel (11), which is to be occupied by the medicament (5) after sterilization, and - introducing energy into the interior (13) of the barrel (11) to sterilize the interior (13) of the barrel (11).

Description

[0001] Medicament Container, Injection Device and Method of Filling the Same

[0002] Description

[0003] Field

[0004] 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.

[0005] Background

[0006] 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.

[0007] 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.

[0008] 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. 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.

[0009] 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.

[0010] 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.

[0011] 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 stored at cryogenic temperatures e.g. minus 196 °C

[0012] 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.

[0013] 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.

[0014] Summary

[0015] In order to solve the above-mentioned problems there is suggested a method of providing and / or filling an aseptic medicament container, a respective medicament container and an injection device comprising such a medicament container as defined by the independent claims, respectively. Further aspects and examples of the present disclosure are subject matter of dependent claims.

[0016] In one aspect the present disclosure relates to a method of providing an aseptic medicament container for filling with a medicament. The method comprises an initial step of providing a barrel comprising a barrel sidewall and comprising an outlet at a distal longitudinal end of the barrel. Then, there is inserted a stopper into the barrel from a longitudinal proximal end of the barrel. The stopper may be inserted only to a limited degree such that there is provided and / or obtained a predefined longitudinal distance between the stopper and the outlet of the barrel.

[0017] An interior of the barrel is then located between the stopper and the outlet and is hence confined by the outlet, the stopper and the sidewall of the barrel. The confined interior is configured or intended for filling with the medicament. The interior of the barrel confined by the stopper, the outlet and the sidewal of the barrel defines a filling volume for the medicament.

[0018] Insofar, the stopper may be inserted or introduced into the barrel only to a limited degree so as to provide sufficient filling space or sufficiently sized interior to be occupied by the medicament later on, e.g. after having prepared and sterilized the empty medicament container.

[0019] After inserting the stopper to a predefined position relative to the barrel there is introduced energy into the interior of the barrel. Introducing energy into the interior of the barrel serves to sterilize the interior of the barrel and hence the empty filling volume of the barrel or medicament container, and to improve a sealing capability of the interface.

[0020] In another example, energy may be also or alternatively introduced into an interface between the stopper and the sidewall, hence, an outside surface of the stopper mechanically engaged with the sidewall may absorb energy, e.g., thermal energy. Introduction of energy into the interface between the stopper and the sidewall may improve a sealing capability of the interface between the stopper and the respective sidewall. In this way, the container closure integrity can be improved. The outlet may be closed or sealed before or during introducing energy into the interior of the barrel. In this way, there can be obtained an empty, closed and sterilized medicament container, which is intended for filling with a liquid medicament under aseptic conditions. Here, and for the process of filling of the medicament container the medicament container does not have to be opened. Filling of the medicament container may be conducted by piercing or penetrating the stopper, e.g., with a filling needle as will be described below.

[0021] In other words, the method of providing the aseptic medicament container includes introducing energy into the interior of the barrel, i.e. to sterilize the interior of the barrel and optionally to introduce energy into the interface between the stopper and the sidewall in order to improve the sealing capability of the interface. In other words, the interior of the barrel is sterilized by introducing energy into the interior. The sealing capability of the interface between the barrel and the stopper can be improved by introducing energy into the interface between the stopper and the sidewall.

[0022] Typically, both effects and both steps of sterilizing the interior and improving the sealing capability of the interface are provided universally by the introduction of energy into the interior and into the interface between the stopper and the sidewall. Introduction or deposition of energy into the interior and into the interface may take place in a temporally overlapping manner. It may take place simultaneously. In this way, the sterilization of the interior of the barrel after stopper insertion may inherently come along with an improvement of the sealing capability of the interface. Moreover, the improvement to the sealing capability of the interface by introducing energy into the interface may be accompanied by a sterilization of the interior of the barrel.

[0023] According to a further example introducing energy into the interior of the barrel and into the interface between the stopper and the sidewall comprises applying electromagnetic radiation into the interior of the barrel and into the interface between the stopper and the sidewall. Electromagnetic radiation applied to the interior of the barrel and applied to the interface, respectively, may be of the same wavelength and / or intensity. Typically, the barrel is translucent or transparent for the electromagnetic radiation. In this way, the interior of the barrel can be exposed to the electromagnetic radiation, which is illuminated from outside the barrel and propagates into the interior. Likewise, the outside surface of the stopper, in particular an outside facing sidewall of the stopper may be easily exposed by the electromagnetic radiation as applied from outside the medicament container or barrel.

[0024] According to a further example ionizing radiation radiation may be used as the (electromagnetic) radiation that is applied or deposited into the interior of the barrel and / or into the interface between the stopper and the sidewall of the barrel. Ionizing radiation may include one of gamma radiation, x-ray radiation or beta radiation. Such ionizing radiation, which is highly energetic, serves to sterilize the interior of the barrel. Moreover, such ionizing radiation may be at least partially absorbed by the outside surface of the sidewall of the stopper and may alter or modify the outside surface of the sidewall of the stopper to improve the sealing capability of the interface between the stopper and the sidewall of the barrel.

[0025] According to some examples, a radiation intensity and / or a type of radiation, e.g., gamma radiation, x-ray radiation or beta radiation is selected or configured to reduce a remaining bioburden, e.g., to obtain an endotoxin level inside the interior at a degree below a predefined lower endotoxin threshold.

[0026] Usually, and in order to breakdown any endotoxins inside the barrel application of thermal energy leading to a temperature of up to 300 °C may be required. Since such temperatures may not be applicable with the presently proposed medicament container or barrel thereof conducting a sterilization and / or improvement to the sealing capability of the interface by way of applying or depositing ionizing electromagnetic radiation may be favorable.

[0027] According to a further example there may be applied laser radiation into the interior of the barrel and / or into the interface. In order to improve the sealing capability of the interface it may be even conceivable to apply ultrasonic waves into the interface in order to deposit energy, e.g. thermal energy into the interface to thereby improve the sealing capability of the interface. Application of laser radiation into the interior or into the interface may be provided in addition to the application of ionizing electromagnetic radiation.

[0028] According to a further example at least one of an outside facing sidewall of the stopper and an inside facing surface of the sidewall of the barrel is at least one of chemically modified, mechanically modified or structurally modified by the introduction of energy, e.g. thermal energy, into the interface between the stopper and the sidewall. Introduction or deposition of energy, e.g., radiation energy, into the interface may serve to improve adherence between the contact surfaces of the outside facing sidewall of the stopper and an inside facing sidewall of the barrel in the interface region.

[0029] Likewise, at least one of the mutually engaging or mutually abutting surfaces of the stopper and the sidewall of the barrel may be structurally modified to improve the sealing capability of the interface. Moreover, deposition or introducing of energy into the interface may lead to changes in the surfaces, namely to changes of material intrinsic properties, which may in turn lead to an improvement of the sealability of the mutually abutting surfaces of the outside sidewall of the stopper and the inside facing sidewall of the barrel.

[0030] According to a further example and after sterilization of the interior and / or after improving of the sealing capability of the interface by the introduction or application of energy the stopper is penetrated by a filling needle and the medicament is introduced into the barrel, e.g. into the interior, via the filling needle. Hence, after the sterilization of the interior and after improving of the sealing capability a method of filling the medicament container may be applied as will be described further below.

[0031] Insofar, all features, effects and benefits as will be described below in connection with the method of filling a medicament container may follow the above-described method of providing and / or preparing an aseptic medicament container.

[0032] The method of filling the medicament container comprises the steps of puncturing the stopper at a puncture site by a filling needle and introducing a medicament into the barrel, specifically into the interior of the barrel by way of the filling needle. Thereafter, the filling needle is withdrawn from the stopper and out of the interior of the medicament container. Finally, the puncture site, i.e. that portion of the stopper that has been punctured by the filling needle, is fused or resealed again. This way, there can be provided a closed and empty medicament container, which is then filled with the medicament by urging the filling needle through the puncturable and re-sealable stopper.

[0033] In this way, a closed but empty medicament container can be manufactured and provided by a container supplier. The closed container after manufacturing is sterilized (e.g., by gamma irradiation) before shipping to the pharmaceutical manufacturer. Such a closed and e.g sterilized medicament container may be then provided to a pharmaceutical manufacturer, who is then conducting the above-mentioned steps of filling the medicament container with a medicament.

[0034] The medicament container, which is pre-assembled and pre-sealed by the outlet and / or via the stopper may be sterilized, e.g. by application of high energetic electromagnetic radiation, e.g. by gamma radiation. In this way, the entirety of the medicament container, e.g. the inside facing surfaces of at least one of the barrel, the outlet and the stopper can be effectively and completely sterilized so as to provide a rather sterile interior of the medicament container before the medicament container is at least partially filled with the medicament. After final sterilization (i.e., gamma) the material properties of all the components and its contact interfaces of the medical container are suitable for its use (e.g., even ensuring container closure integrity at cryogenic - storage temperatures)

[0035] Of course, puncturing of the stopper by way of the filling needle may harm the integrity of the stopper and may deteriorate its original sealing capability. However, and by way of fusing or resealing the puncture site, such negative effects that may eventually arise from the puncturing of the stopper, can be at least compensated or even over-compensated by the fusing or resealing. Stoppers may be made of thermoplastic elastomers or from other suitable materials.

[0036] According to a further example the stopper is at least temporarily immobilized relative to the barrel before and / or during the stopper being punctured by the filling needle. Immobilizing the stopper relative to the barrel is of particular benefit to avoid any movement of the stopper relative to the barrel when mechanically engaged with the filling needle. Otherwise, the container closure integrity could be impaired, e.g. by a disruption of the interface between the stopper and the barrel.

[0037] Deposition of energy into the interface between the stopper and the sidewall of the barrel may further support an at least temporarily immobilization of the stopper relative to the sidewall of the barrel. Depending on the choice of materials for the stopper and the barrel, the deposition of energy into the interface between the stopper and the sidewall of the barrel may support or lead to a mutual fusing of the stopper and the sidewall. Hence, improving the sealing capability of the interface by the deposition of energy into the interface before, during or after conducting a sterilization of the interior of the medicament container, may provide or may support a mutual fixing between the sidewall of the barrel and the stopper. Hence and due to the improvement of the sealing capability a break loose force for moving the plunger relative to the sidewall of the barrel may be substantially increased.

[0038] In some examples there may be provided a support structure for fixing the stopper. There may be further provided a further support structure for fixing the barrel. By fixing the above- mentioned support structure and the further support structure relative to each other there may be provided a relative fixing between the stopper and the barrel of the medicament container.

[0039] Hence, prior and / or at least during the puncturing of the stopper by the filling needle the barrel may be immobilized relative to and / or by a first support structure and the stopper may be immobilized or fixed relative and / or by a second support structure, wherein the second support structure is positionally fixed relative to the first support structure; and vice versa. In this way there can be provided a relative positional fixing of the stopper relative to the barrel. The support structures may be configured to fix at least one of the stopper and the barrel with regard to the longitudinal direction of the barrel. The support structure for fixing the stopper may be configured to fix the stopper with regard to the longitudinal distal direction as well as with regard to the longitudinal proximal direction. The further support structure may be configured for fixing the barrel with regard to the longitudinal distal direction as well as with regard to the longitudinal proximal direction. In this way, the stopper and / or the barrel may be longitudinally fixed even when subject to a distally directed force effect, e.g. when the stopper is penetrated by the filling needle in distal direction. The stopper and the barrel may be longitudinally fixed when subject to a proximally directed force effect, e.g. when the filling needle is retracted in proximal direction out of the stopper.

[0040] During a piercing or puncturing of the stopper by the filling needle it may be thus ensured, that the stopper does not move relative to the barrel. The container closure integrity as initially provided may be thus maintained. The filling needle, e.g. a cannula and bevels, may be customized to allow air venting during filling and to avoid the stopper movement.

[0041] According to a further example the stopper comprises a distal side and a proximal side. The distal side faces towards the distal longitudinal end of the barrel. The proximal side faces towards the proximal longitudinal end of the barrel. The stopper further comprises a fastening structure at the proximal side for fastening to a plunger. The stopper may be fastened to the plunger and is at least temporarily immobilized relative to the barrel through or by way of the plunger. Hence, the plunger may provide a fastening and mechanical coupling to the stopper when the stopper is located inside the barrel of the medicament container.

[0042] The stopper is typically accessible from a proximal end of the barrel of the medicament container. Hence, the plunger may be introduced into or through the proximal end of the barrel until it mechanically engages with the proximal side of the stopper. When the plunger is mechanically engaged with the stopper, e.g. by engaging the plunger with the fastening structure as provided at or on the proximal side of the stopper, the stopper may be hindered to move in distal direction, hence towards the outlet, as long as the plunger is hindered or blocked from a distally directed motion. Hence, a mutual connection between the stopper and the plunger is tensional stable or tension resistant.

[0043] Hence, a distally directed force effect acting on the stopper may unalterably transfer to the plunger. Likewise, a proximally directed force effect acting on the plunger may be unalterably transferable or may be unalterably transferred to the stopper. In this way, any eventual and distally directed forces as applied by the filling needle onto the stopper, e.g., in the course of puncturing the stopper, may be counteracted by the plunger connected and / or fixed to the stopper.

[0044] According to a further example the plunger comprises a counter fastening structure to connect to the fastening structure at the proximal side of the stopper. The plunger is fastened to the stopper by fastening the counter fastening structure of the plunger to the fastening structure of the stopper before the stopper is punctured by the filling needle. In this way, there can be provided a rather stable and well-defined mutual connection and fixing between the stopper and the plunger. Moreover, and by maintaining a longitudinal position of the plunger relative to the barrel the stopper is hindered to move relative to the barrel, e.g. during a puncturing with the filling needle.

[0045] According to a further example the plunger comprises a longitudinally extending guiding structure. The filling needle is guided along this longitudinally extending guiding structure for puncturing the stopper.

[0046] The longitudinally extending guiding structure may extend all along the longitudinal extent or longitudinal elongation of the plunger. The guiding structure may extend through the entirety of the plunger and may thus provide unhindered access to the proximal side of the stopper. The longitudinally extending guiding structure may also provide a well-defined longitudinal guiding of the filling needle at and / or along the plunger. In this way, and when inserting the filling needle into the barrel from a proximal end of the barrel towards the distal direction the longitudinally extending guiding structure may provide a rather well-defined longitudinal and hence transverse guiding of the filling needle, thereby also defining a well-defined puncture site of the stopper to be pierced or to be punctured by a distally located end of the filling needle.

[0047] According to a further example the longitudinally extending guiding structure comprises a hollow channel extending in a longitudinal direction. The filling needle is hence guided in longitudinal distal direction through the hollow channel. The radial extent or cross-section of the hollow channel is at least slightly larger than a respective radial extent or diameter or cross-section of the filling needle. In this way, the filling needle can be effectively guided by the hollow channel of the plunger.

[0048] In other words, the plunger provides a twofold function. First of all, it may provide a fixing of the stopper relative to the barrel during puncturing as well as during filling of the interior volume of the medicament container with a medicament to. Second, the plunger may also provide a lateral and hence longitudinal guiding for the filling needle, so as to hit a well-defined radial position of the stopper.

[0049] The hollow channel of the longitudinally extending guiding structure of the plunger may further provide a well-defined sealing or fusing of the puncture site after removal of the filling needle from the stopper.

[0050] According to a further example the plunger comprises a proximal end with an insert opening to receive the filling needle. The insert opening may be finally closed and / or sealed by a supplemental closure. The insert opening may be closed by the supplemental closure after fusing of the puncture site. Use of a further closure to close the hollow channel is beneficial to improve the container closure integrity and to protect the proximal side of the stopper against environmental influences, such as humidity or other contaminants, e.g. dust.

[0051] Closing the insert opening, e.g. at a proximal end of the plunger may improve the general handling of the plunger, e.g. for a subsequent injection of a dose of the medicament from the medicament container. Hence, the closure configured to close the insert opening of the plunger may form part of a thrust or pressure receiving face, e.g. at a proximal end of the plunger, e.g. provided with a plunger flange.

[0052] According to a further example the puncture site it is fused or resealed by directing a laser beam from the proximal longitudinal end of the medicament container onto the puncture site. Typically, the laser beam is directed in distal direction into and / or through the proximal end of the barrel. When the plunger is permanently fixed to the stopper the laser beam may be also directed through the hollow channel and along the longitudinally extending guiding structure of the plunger to reach the proximal side of the stopper and / or to align with the puncture site. Insofar, the hollow channel and / or the longitudinally extending guiding structure of the plunger provides a further function, namely to guide a laser beam there through.

[0053] The environment for conducting assembling of the medicament container components may fulfill ISO 5 and / or ISO 7 clean room classifications. Sterilization of the interior of the barrel may be provided by applying high intensity electromagnetic radiation, e.g. gamma radiation, and may determine the material properties of the components and interfaces. After that, the closed and sterile medicament container can be shipped to the pharmaceutical manufacturer for filling with the liquid drug product.

[0054] According to a further example an interior of the barrel, which is confined by the barrel sidewall, by the outlet and by the stopper is sterilized before the stopper is punctured by the filling needle. Moreover, the filling of the medicament container may be conducted in a protected or enclosed environment. The environment for filling of the medicament container may fulfill predefined demands and requirement for filling conditions. The environment for conducting the method of filling the medicament container may fulfill ISO 5 and / or ISO 7 clean room classifications.

[0055] According to a further aspect the present disclosure also relates to an aseptic medicament container for filling with a medicament. The medicament container comprises a barrel with a barrel sidewall. The medicament container further comprises an outlet at a distal longitudinal end of the barrel. The medicament container further comprises a stopper, which is located inside the barrel and which is movable relative to the barrel. The stopper seals an interior of the barrel towards a proximal longitudinal end. The stopper is located at a predefined longitudinal distance from the outlet and hence from the distal end of the barrel to confine an interior and hence an empty filling space or empty filling volume of the medicament container.

[0056] The interior of the barrel is sterilized by introducing energy into the interior of the barrel. The sealing capability of an interface between the stopper and the sidewall may be also improved by the introduction of energy into the interface. Introduction of energy into the interior of the barrel and / or into the interface between the stopper and / or into the sidewall modifies the structure of the aseptic medicament container. Hence, the medicament container is or can be characterized by an interior, which has been sterilized by energy introduction. The aseptic medicament container may be further characterized by improved sealing capabilities of the interface between the stopper and the barrel, which are provided by energy introduction or energy deposition into the interface.

[0057] In some examples the aseptic medicament container is obtained by conducting the abovedescribed method of providing an aseptic medicament container. Insofar, all effects, features and benefits as described above in connection with the method of providing an antiseptic medicament container equally apply to the aseptic medicament container as described herein; and vice versa.

[0058] According to a further example, the interior of the barrel confined by the sidewall of the barrel, by the stopper and by the outlet, is sterilized and is empty. The so-confined interior of the barrel may define the filling volume and hence the size of an empty space, which is configured to receive or to accommodate a predefined amount of a medicament, e.g., of an injectable liquid medicament.

[0059] According to a further example at least one of an outside facing sidewall of the stopper and an inside facing surface of the sidewall of the barrel is at least one of chemically modified, mechanically modified or structurally modified by the introduction of energy into the interface between the stopper and the sidewall. The chemical, mechanical and / or structural modification is an immediate or indirect result of the energy deposition into the interface and may thus lead to an improved sealing capability of the interface.

[0060] According to a further example at least one of the interior of the barrel and the interface between the stopper and the sidewall have been subject to introduction of energy through irradiation with electromagnetic radiation. The interior and / or the interface of medicament container may have been subject to introduction of energy through irradiation with ionizing radiation, e.g. gamma radiation, x-ray radiation or beta radiation. Here, application of gamma radiation serves two separate purposes, namely to sterilize the interior of the barrel of the medicament container and to improve the sealing capability of the interface between the stopper and the sidewall of the barrel.

[0061] According to a further example the barrel is made of a polymeric material, in particular of a cyclic-olefin polymer (COP) material or is made of a cyclic-olefin copolymer (COC) material. These materials may be substantially transparent for electromagnetic radiation, at least in the gamma radiation spectrum. In this way, the medicament container can be irradiated from outside without significant radiation losses.

[0062] Moreover, an outside surface, e.g. a sliding surface or gliding surface of the sidewall of the stopper may absorb a significant amount of the electromagnetic radiation, which is sufficient to modify or to alter the surface and / or the sidewall of the stopper chemically, mechanically and / or structurally in order to improve the sealing capability with the inside surface of the sidewall of the barrel.

[0063] According to another example the stopper comprises or is made of a thermoplastic elastomeric material. Such materials, especially in combination with a polymeric material of the barrel may provide a comparatively good or even excellent container closure integrity when the medicament container is stored at comparatively low temperatures (< 0° C), at ultra-low temperatures (< -60° C) or even at cryogenic temperatures (< -196° C).

[0064] Accordingly, the aseptic medicament container may be configured for medicament storage at low temperatures, at ultra-low temperatures or even at cryogenic temperatures. Here, the chemically, mechanically or structurally modified sidewall of the stopper may provide a container closure integrity even at such low temperatures. However, the stopper may or must not be moved in longitudinal direction during storage of the aseptic medicament container at particularly low temperatures.

[0065] According to a further example the interior of the barrel, which is confined by the sidewall of the barrel, by the stopper and by the outlet, is empty. The aseptic medicament container is configured for filling with a medicament thereafter, e.g. after sterilization, which sterilization is conducted by application of electromagnetic radiation after closing the proximal end of the barrel with the stopper and, of course, after the outlet of the barrel is closed.

[0066] The aseptic medicament container for filling with a medicament as described herein may be used with a method of filling a medicament container as described above. Insofar, all features, effects and benefits as described above in connection with the method of filling a medicament container may apply to the above-described medicament container prepared for filling with the medicament in order to provide the above-mentioned or above-described medicament container, which is configured for use with an injection device.

[0067] According to another example the interior of the barrel of the aseptic medicament container is filled with a medicament, which has been introduced into the barrel by a filling needle penetrating the stopper.

[0068] In a further aspect the present disclosure also relates to another medicament container for use in or with an injection device. The medicament container comprises a barrel with a barrel sidewall. The medicament container further comprises an outlet at a distal longitudinal end of the barrel. The medicament container further comprises a stopper located inside the barrel and being movable relative to the barrel. The stopper is configured to seal the barrel towards a proximal longitudinal end. In some examples the stopper actually seals the barrel towards the proximal longitudinal end of the barrel. The stopper of the medicament container is puncturable at a puncture site by a filling needle. In some examples the stopper may be puncturable everywhere by a respective filling needle.

[0069] The puncture site may be an arbitrary site or position on a proximal side of the stopper, e.g. accessible from a proximal end of the stopper or barrel. The puncture site is fusable or re- sealable after puncturing with the filling needle and after the filling needle has been withdrawn from the puncture site. Typically, the filling needle comprises a tipped distal end. It may comprise a sharp bevel point with a blade-like shape, which is operable to cut through the material of the stopper. It may have features on the cannula and / or more than one channel to allow filling and air venting. The medicament container as described herein is particularly suitable to conduct the method of filling a medicament container as described above. Insofar, all effects, features and benefits as described above in connection with the method of filling the medicament container equally apply to the medicament container; and vice versa.

[0070] According to a further example the puncture site has been punctured by the filling needle and the puncture site is fused to re-seal the punctured puncture site. In other words and when the medicament container is filled, the medicament inside the barrel has been introduced and filled into the interior of the medicament container by piercing the plunger with a filling needle and by introducing or depositing the medicament through the filling needle into the interior of the medicament container. When the medicament container is stored and / or delivered to consumers or patients the puncture site of the stopper has been punctured by the filling needle and the respective puncture site arising from the filling needle-based puncturing is fused or resealed, e.g. by applying thermal energy onto the puncture site, e.g. by way of a laser beam.

[0071] According to a further example the medicament container comprises a plunger connectable or connected to a fastening structure at a proximal side of the stopper. The plunger comprises a longitudinally extending guiding structure to guide the filling needle for puncturing the stopper and / or for filling the interior of the medicament container with a medicament, e.g. with a liquid medicament. The plunger, e.g. a proximal end of the plunger may protrude from the proximal end of the barrel. In this way and by connecting the plunger to the stopper the longitudinal position of the stopper relative to the barrel can be controlled via the plunger. This allows for an at least temporal immobilization of the stopper relative to the barrel, e.g. before or during puncturing of the stopper with the filling needle.

[0072] According to a further example the longitudinally extending guiding structure comprises a hollow channel extending in a longitudinal direction to guide the filling needle in a longitudinal distal direction and / or longitudinal proximal direction. In this way, the filling needle can be precisely guided through the hollow channel of the plunger so as to hit a well-defined or predefined puncture site at the proximal side of the stopper. When the plunger is fastened or fixed to the stopper and when the filling needle is guided through the longitudinal guiding structure of the plunger, the longitudinal movement of the filling needle relative to the plunger and hence relative to the stopper can be easily controlled.

[0073] In a further example at least one of the longitudinally extending guiding structure and the hollow channel of the plunger is sealed in the longitudinal distal direction by the stopper. Hence, the stopper may effectively close an outlet end of the hollow channel and a distal end of the plunger. In this way, and when there is provided a rather well defined and stable mutual fixing between the stopper and the plunger it can be effectively guaranteed, that the filling needle entering or moving through the hollow channel of the longitudinally extending guiding structure of the plunger hits the stopper in a well-defined manner.

[0074] According to a further example the plunger comprises a counter fastening structure connectable or connected to the fastening structure of the stopper. Here, the fastening structure and the counter fastening structure are configured to form one of a positive connection, a non-positive connection, a welded connection and an adhesive connection between the plunger and the stopper.

[0075] In some examples the plunger and the stopper may be made of a single piece. Hence, the plunger and the stopper may be integrally or unitarily formed and may be made from the same material, e.g., by an over-molding or 2K-molding process. With such solutions, the plunger and the stopper may not have to be mutually connected and fixed. They may be inherently immobilized relative to each other by way of their integral or single-pieced manufacturing.

[0076] Generally, and when the plunger and the stopper are made of different materials the fastening structure and the counter fastening structure may form or constitute at least one of a positive connection, a non-positive connection, a welded or adhesive connection. In some examples, the stopper may comprise a thermoplastic elastomeric material or other suitable materials, which may enable and support a laser welding process for resealing the puncture spot). Also the plunger may comprise a thermoplastic material. The plunger and the stopper may be mutually fastened by way of a welding or by way of an adhesive. In other examples the distal end of the plunger may comprise a first part of a positive connection and the proximal side of the stopper may comprise a second part of a positive connection, wherein the first and the second parts of the positive connection may be complementary shapes so as to form the positive connection when the plunger is brought in engagement, i.e. mechanical engagement with the stopper.

[0077] Here, the fastening structure may comprise a thread and the counter fastening structure may comprise a complementary shaped counter thread. With other solutions there may be provided a friction fit between the fastening structure and the counter fastening structure or the like non- positive connection.

[0078] According to a further example the plunger comprises a proximal end with an insert opening for the filling needle. The insert opening is closed and / or sealed by a closure. Typically and before or during filling of the medicament container by way of the filling needle intersecting the stopper, the insert opening of the plunger is open and is hence fully accessible for the filling needle. It is only after withdrawal of the filling needle in proximal direction from the plunger that the insert opening of the proximal end of the plunger is closed and / or sealed by a closure. In this way, the hollow channel extending between the insert opening and a distal end of the plunger is effectively sealed against any environmental influences.

[0079] The hollow channel as provided by the longitudinally extending guiding structure of the plunger may comprise a rather closed structure, which is void of any radial through openings or the like perforations. Insofar and by closing a distal end of the hollow channel by the stopper and by closing a proximal end of the hollow channel and / or a proximal end of the insert opening of the plunger, the interior of the plunger, which is in direct contact with a portion of the proximal side of the stopper, can be effectively sealed against ingress of any contaminants or the like substances.

[0080] According to a further example the closure comprises a planar-shaped lid portion. The lid portion flushes with a proximal end of the plunger when the insert opening is closed or sealed by the enclosure. Typically, the proximal end of the plunger may comprise a radially widened plunger flange. By arranging the lid portion to the proximal end of the plunger a respective insert opening can be effectively closed and sealed. At the same time the lid portion of the closure may contribute to a pressure- or thrust-receiving face by way of which a user may apply a distally directed pressure onto the plunger for urging the plunger in distal direction relative to the barrel, e.g. in the course or during delivery or injection of the medicament.

[0081] According to another example the closure comprises an elongated stem protruding from an inside surface of the lid portion. The elongated stem is configured for insertion into the hollow channel of the plunger. In some examples an outside diameter or outer cross-section of the stem may correspond to a respective inner a diameter or inside cross-section of the hollow channel of the plunger. In this way, and by inserting the elongated stem into the hollow channel of the plunger the lid portion and hence the entire closure can be self-centered with regard to a radial direction.

[0082] According to a further example the plunger comprises an elongated plunger rod and a plunger flange provided at a proximal end of the plunger rod. The plunger flange comprises a receptacle to receive the closure. Typically, the receptacle comprises a radial extent or inside diameter or cross-section that is substantially larger than a respective radial extent or radial cross-section of the hollow channel adjoining the receptacle in distal direction. The receptacle may be shaped to receive the entirety of the planar-shaped lid portion. The longitudinal size of the receptacle, which may be confined by a longitudinally extending and surrounding sidewall may correspond with a longitudinal thickness of the planar-shaped lid portion. Accordingly, an inside surface of the lid portion of the closure may abut a bottom portion of the receptacle as provided at the proximal end of the receptacle of the plunger. When the longitudinal extent of the lid portion matches or corresponds to the longitudinal depth of the receptacle an outside surface of the planar -shaped lid portion may flush with a proximal end face of a sidewall of the receptacle thereby providing a rather smooth planar shaped proximal end of the plunger flange at the proximal end of the plunger.

[0083] According to a further example the barrel comprises a barrel flange at the proximal longitudinal end which barrel flange protrudes radially outwardly from the barrel sidewall. By way of such a barrel flange, a general handling of the medicament container can be facilitated and simplified. Providing of a radially outwardly extending barrel flange at the proximal end of the barrel sidewall may act or behave as a syringe flange. The barrel flange may comprise an annular structure, e.g. featuring a completely closed circumference extending around the outside surface of the sidewall of the barrel. In some examples the barrel flange may comprise a first flange portion and a second central portion radially opposite to the first flange portion. Here, the barrel flange may be provided only at a dedicated portion along an outer circumference of the sidewall of the barrel.

[0084] According to a further example the barrel is made of a polymeric material. The barrel may comprise a cyclo-olefin copolymer (COC) material. In some examples the entirety of the barrel may be made of such a material. Such materials exhibit an excellent compatibility and are effectively inert to a large number of medicaments. At the same time such materials may be provided as a transparent material so as to enable visual inspection of the interior of the medicament container from outside the medicament container.

[0085] According to a further example the stopper comprises or is made of a thermoplastic elastomer material.

[0086] In some examples, the coefficient of thermal expansion of the material of the barrel and of the material of the stopper may be substantially identical or may mutually match. In some examples the material for the stopper and the material for the barrel of the medicament container match with regards to their coefficient of thermal expansion especially in the region of comparatively low temperatures or ultra-low temperatures, e.g. below -60°C. In this way there can be provided an excellent container closure integrity even when the medicament container is stored under such conditions.

[0087] According to a further example the medicament container provides a container closure integrity at a storage temperature below -40°C, -50°C or even below -60°C. In further examples the medicament container provides an intact container closure integrity even at storage temperatures below -80°C or below -196°C.

[0088] In some examples the barrel comprises or is made of a polymeric or plastic material and the stopper is made of or comprises a thermoplastic elastomer material. This material combination is particularly suitable for a storage of the medicament container at the above-mentioned low temperatures or ultra-low temperatures or even at cryogenic temperatures.

[0089] In other examples, the barrel may comprise a vitreous material and the stopper may comprise an elastomeric material, such as synthetic or natural rubber. This material combination may also provide container closure integrity. Typically, a material combination of glas and rubber for the barrel and for the stopper, respectively, may be used for storage above -10 °C, above -5°C, above 0°C and / or above 5 °C.

[0090] Specifically and when the stopper comprises an elastomeric material an immobilization of the stopper relative to the barrel may not be necessary during or for puncturing of the stopper by the filling needle. The steps of puncturing the stopper with the filling needle, introducing the medicament into the barrel via the filling needle and / or withdrawing the filling needle from the stopper may be accompanied by a movement of the stopper relative to the barrel and may be thus tolerable. Elastomeric stoppers may provide a sufficient container closure integrity even when subject to a longitudinally directed movement relative to the sidewall of the barrel.

[0091] Here, the stopper could be positioned at or near the distal end of the barrel. When filling the container, e.g. via the filling needle penetrating the stopper, the stopper might move backwards, i.e. in proximal direction into its final position.

[0092] According to another example the medicament container comprises a pierceable seal at the outlet. Here, the medicament container may be provided as a cartridge, e.g. as a multi-dose cartridge. The pierceable seal may be punctured by an injection needle, e.g. when the medicament container is used with a pen-type injector or the like injection device. The pierceable seal may be penetrated by the injection needle in the course of mounting or attaching the injection needle to at least one of the medicament container and / or to a housing of an injection device, in which the medicament container is accommodated. According to a further example the medicament container comprises a cartridge, e.g. a multidose cartridge. The cartridge is sealed in distal direction by a pierceable seal, e.g. fixed to a distal end of the barrel by a crimped metal cap.

[0093] In a further example the injection device comprises an injection needle at the outlet or protruding through the outlet of the medicament container. The injection needle may comprise a proximal end located inside the interior of the medicament container or being in fluid connection with the interior of the medicament container. The injection needle may comprise a distal end, typically a tipped distal end configured for piercing biological tissue. The injection needle may be permanently fixed to the outlet or may constitute the outlet of the medicament container. It may be fused or welded in a distally located section of the barrel or of the barrel outlet.

[0094] In some examples, the barrel may comprise a radially narrowing structure towards its distal end. It may comprise a radially narrowing shoulder portion and a radially narrowed neck portion. The injection needle may be provided in the neck portion and may protrude in distal direction from a distal end of the barrel. The injection needle may be non-movably fixed to the barrel or to the outlet of the medicament container.

[0095] According to another example the injection device comprises a connector at the outlet. The connector may be configured for connecting to a complementary shaped counter connector in a fluid transferring manner. The connector may comprise a standardized connection, e.g. a standardized liquid transferring connection for transferring a liquid medicament inside the medicament container into an infusion line or the like. In some examples the connector may comprise a Luer connector or Luer fitting.

[0096] A connector of the injection device connected to the counter connector of a fluid guiding structure can be used to provide a standardized fluid transferring connection between the injection device and the fluid guiding structure, such as an infusion line.

[0097] According to another example the injection device comprises a pre-filled syringe. In other words, the injection device is implemented as a pre-filled syringe.

[0098] Generally, the scope of the present disclosure is defined by the content of the claims. 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.

[0099] It is further to be noted that the present disclosure is in no way limited by the claims or by the above and below described examples. Moreover, numerous variations of the medicament container and methods of filling or preparing the medicament container are within the present disclosure. These variations will be defined and will be apparent by the following clauses and their mutual combinations.

[0100] Clause 1. A method of filling a medicament container (10), the medicament container (10) comprises: a barrel (11) with a barrel sidewall (12), an outlet (14) at a distal longitudinal end (15) of the barrel (11) and a stopper (20) located inside the barrel (11), movable relative to the barrel (11) and sealing the barrel (11) towards a proximal longitudinal end (16), the method of filling the medicament container comprises the steps of: puncturing the stopper (20) at a puncture site (22) by a filling needle (30), introducing a medicament (5) into the barrel (11) via the filling needle (30), withdrawing the filling needle (30) from the stopper (20) and fusing the puncture site (22).

[0101] Clause 2. The method according to clause 1 , wherein the stopper (20) is at least temporarily immobilized relative to the barrel (11) before and / or during the stopper (20) is punctured by the filling needle (30).

[0102] Clause 3. The method according to clause 1 or 2, wherein the stopper (20) comprises a distal side (25) and a proximal side (26), wherein the distal side (25) faces towards the distal longitudinal end (15) of the barrel (11) and wherein the proximal side (26) faces towards the proximal longitudinal end (16) of the barrel (11) and wherein the stopper (20) comprises a fastening structure (24) at the proximal side (26) for fastening to a plunger (40) and wherein the stopper (20) is fastened to the plunger (40) and is at least temporarily immobilized relative to the barrel (11) through the plunger (40).

[0103] Clause 4. The method according to clause 3, wherein the plunger (40) comprises a counter fastening structure (44) to connect to the fastening structure (24) at the proximal side (26) of the stopper (20) and wherein the plunger (40) is fastened to the stopper (20) by fastening the counter fastening structure (44) of the plunger (40) to the fastening structure (24) of the stopper (20) before the stopper (20) is punctured by the filling needle (30). Clause 5. The method according to clause 3 or 4, wherein the plunger (40) comprises a longitudinally extending guiding structure (41) and wherein the filling needle (30) is guided along the longitudinally extending guiding structure (41) for puncturing the stopper (20).

[0104] Clause 6. The method according to clause 5, wherein the longitudinally extending guiding structure (41) comprises a hollow channel (42) extending in a longitudinal direction (z) and wherein the filling needle (30) is guided in longitudinal distal direction (2) through the hollow channel (42).

[0105] Clause 7. The method according to clause 5 or 6, wherein the plunger (40) comprises a proximal end (46) with an insert opening (47) to receive the filling needle (30) and wherein the insert opening (47) is closed and / or sealed by a closure (50) after fusing of the puncture site (22).

[0106] Clause 8. The method according to any one of the preceding clauses, wherein the puncture site (22) is fused by directing a laser beam (28) from the proximal longitudinal end (16) onto the puncture site (22).

[0107] Clause 9. The method according to any one of the preceding clauses, wherein an interior (13) of the barrel (11) confined by the barrel sidewall (12), by the outlet (14) and by the stopper (20) is sterilized before the stopper is punctured by the filling needle (30).

[0108] Clause 10. A medicament container (10) for use with an injection device (1), the medicament container comprising: a barrel (11) with a barrel sidewall (12), an outlet (14) at a distal longitudinal end (15) of the barrel (11) and a stopper (20) located inside the barrel (11), movable relative to the barrel (11) and sealing the barrel (11) towards a proximal longitudinal end (16), wherein the stopper (20) is puncturable at a puncture site (22) by a filling needle (30), and wherein the puncture site (22) is fusable after puncturing with the filling needle (30) and after withdrawing of the filling needle (30) from the puncture site (22).

[0109] Clause 11. The medicament container (10) according to clause 10, wherein the puncture site (22) has been punctured by the filling needle (30) and wherein the puncture site (22) is fused to re-seal the punctured puncture site (22). Clause 12. The medicament container (10) according to clause 10 or 11 , further comprising a plunger (40) connectable or connected to a fastening structure (24) at a proximal side (26) of the stopper (20), wherein the plunger (40) comprises a longitudinally extending guiding structure (41) to guide the filling needle (30) for puncturing the stopper (20).

[0110] Clause 13. The medicament container (10) according to clause 12, wherein the longitudinally extending guiding structure (41) comprises a hollow channel (42) extending in a longitudinal direction (z) to guide the filling needle (30) in a longitudinal distal direction (2).

[0111] Clause 14. The medicament container (10) according to clause 12 or 13, wherein at least one of the longitudinally extending guiding structure (41) and the hollow channel (42) is sealed in the longitudinal distal direction (2) by the stopper (20).

[0112] Clause 15. The medicament container (10) according to any one of the preceding clauses 12-14, wherein the plunger (40) comprises a counter fastening structure (44) connectable or connected to the fastening structure (24) of the stopper (20), wherein the fastening structure (24) and the counter fastening structure (44) are configured to form at least one of a positive connection, a non-positive connection, a welded connection and an adhesive connection between the plunger (40) and the stopper (20).

[0113] Clause 16. The medicament container (10) according to any one of the preceding clauses 12-15, wherein the plunger (40) comprises a proximal end (46) with an insert opening (47) for the filling needle (30), wherein the insert opening (47) is closed and / or sealed by a closure (50).

[0114] Clause 17. The medicament container (10) according to clause 16, wherein the closure (50) comprises a planar-shaped lid portion (51), which flushes with the proximal end (46) of the plunger (40) when the insert opening (47) is closed or sealed by the closure (50).

[0115] Clause 18. The medicament container (10) according to clause 16 or 17, wherein the closure

[0116] (50) comprises an elongated stem (52) protruding from an inside surface (53) of the lid portion

[0117] (51), wherein the elongated stem (52) is configured for insertion into the hollow channel (42) of the plunger (40).

[0118] Clause 19. The medicament container (10) according to any one of the preceding clauses 16-18, wherein the plunger (40) comprises an elongated plunger rod (43) and a plunger flange (45) provided at a proximal end of the plunger rod (43), wherein the plunger flange (45) comprises a receptacle (48) to receive a closure (50). Clause 20. The medicament container (10) according to any one of the preceding clauses 10-19, wherein the barrel (11) comprises a barrel flange (17) at the proximal longitudinal end (16) protruding radially outwardly from the barrel sidewall (12).

[0119] Clause 21. The medicament container (10) according to any one of the preceding clauses

[0120] 10-20, wherein the barrel (11) is made of a polymeric material, in particular of a cyclo-olefin polymer (COP) material or cyclo-olefin copolymer (COC) material.

[0121] Clause 22. The medicament container (10) according to any one of the preceding clauses 10-20, wherein the barrel (11) is made of a vitreous material comprises a vitreous material.

[0122] Clause 23. The medicament container (10) according to any one of the preceding clauses 10-22, wherein the stopper (20) comprises or is made of a thermoplastic elastomer (TPE) material.

[0123] Clause 24. The medicament container (10) according to any one of the preceding clauses 10-22, wherein the stopper (20) comprises or is made of an elastomeric material.

[0124] Clause 25. The medicament container (10) according to any one of the preceding clauses, wherein the medicament container (10) provides a container closure integrity at a storage temperature below -40°C, below -50°C, below -60°C or below -196°C.

[0125] Clause 26. The medicament container (10) according to any one of the preceding clauses, further comprising a pierceable seal (19) at the outlet (14).

[0126] Clause 27. The medicament container (10) according to clause 26, wherein the medicament container (10) comprises a cartridge.

[0127] Clause 28. An injection device (1) for injecting a liquid medicament (5) into biological tissue, the injection device comprising a medicament container (10) according to any one of the preceding clauses 10-27.

[0128] Clause 29. The injection device (1) according to clause 28, further comprising an injection needle (6) at the outlet (14) or protruding through the outlet (14). Clause 30. The injection device (1) according to clause 28, further comprising a connector (18) at the outlet (14), wherein the connector (18) is configured for connecting to a complementary shaped counter connector in a fluid-transferring manner.

[0129] Clause 31 . The injection device (1) according to any one of the preceding clauses 28-30, wherein the injection device (1) comprises a pre-filled syringe (4).

[0130] Clause 32. A method of providing an aseptic medicament container (10) for filling with a medicament (5), the method comprising: providing a barrel (11) with a barrel sidewall (12) and comprising an outlet (14) at a distal longitudinal end (15) of the barrel (11), inserting a stopper (20) into the barrel (11) from a longitudinal proximal end (16) of the barrel (11) and introducing energy into the interior (13) of the barrel (11) and into an interface (29) between the stopper (20) and the sidewall (12) to sterilize the interior (13) of the barrel (11) and to improve a sealing capability of the interface (29).

[0131] Clause 33. The method according to clause 32, wherein introducing energy into the interior (13) of the barrel (11) and into the interface (29) between the stopper (20) and the sidewall (12) comprises applying electromagnetic and / or ionizing radiation (60) into the interior (13) of the barrel (11) and into the interface (29) between the stopper (20) and the sidewall (12).

[0132] Clause 34. The method according to clause 32 or 33, wherein gamma radiation is applied into the interior (13) of the barrel (11) and into the interface (29) between the stopper (20) and the sidewall (12).

[0133] Clause 35. The method according to any one of the preceding clauses 32-34, wherein at least one of an outside facing sidewall (21) of the stopper (20) and an inside facing surface of the sidewall (12) of the barrel (11) is at least one of chemically, mechanically or structurally modified by the introduction of energy into the interface (29) between the stopper (20) and the sidewall (12).

[0134] Clause 36. The method according to any one of the preceding clauses 32-35, wherein after sterilization of the interior (13) and after improving of the sealing capability of the interface (29) the stopper (20) is penetrated by a filling needle (30) and the medicament (5) is introduced into the barrel (11) via the filling needle (30). Clause 37. An aseptic medicament container (10) for filling with a medicament (5), the medicament container (10) comprising: a barrel (11) with a barrel sidewall (12), an outlet (14) at a distal longitudinal end (15) of the barrel (11) and a stopper (20) located inside the barrel (11), movable relative to the barrel (11) and sealing an interior (13) of the barrel (11) towards a proximal longitudinal end (16), wherein the interior (13) of the barrel (11) is sterilized by introducing energy into the interior (13) and wherein a sealing capability of an interface (29) between the stopper (20) and the sidewall (12) is improved by the introduction of energy into the interface (29).

[0135] Clause 38. The medicament container (10) according to clause 37, wherein at least one of an outside facing sidewall (21) of the stopper (20) and an inside facing surface of the sidewall (12) of the barrel (11) is at least one of chemically, mechanically or structurally modified by the introduction of energy into the interface (29) between the stopper (20) and the sidewall (12).

[0136] Clause 39. The medicament container (10) according to any one of the preceding clauses 37 or 38, wherein at least one of the interior (13) of the barrel (11) and the interface (29) between the stopper (20) and the sidewall (12) has been subject to introduction of energy through irradiation with electromagnetic radiation (60).

[0137] Clause 40. The medicament container (10) according to any one of the preceding clauses 37-39, wherein the barrel (11) is made of a polymeric material, in particular of a cyclo-olefin polymer (COP) material or cyclo-olefin copolymer (COC) material.

[0138] Clause 41. The medicament container (10) according to any one of the preceding clauses 37-40, wherein the stopper (20) comprises or is made of a thermoplastic elastomer (TPE) material.

[0139] Clause 42. The medicament container (10) according to any one of the preceding clauses 37-41, wherein the interior (13) of the barrel (11) confined by the sidewall (12), by the stopper (20) and by the outlet (14) is empty.

[0140] Clause 43. The medicament container (10) according to any one of the preceding clauses 37-41, wherein the interior (13) of the barrel (11) is filled with a medicament (5), which has been introduced into the barrel (11) via a filling needle (30) penetrating the stopper (20). In the present context the term ‘distal’ or ‘distal end’ relates to an end of the injection device that faces towards an injection site of a person or of an animal. The term ‘proximal’ or ‘proximal end’ relates to an opposite end of the injection device, which is furthest away from an injection site of a person or of an animal.

[0141] 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.

[0142] 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.

[0143] 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.

[0144] 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.

[0145] 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, 15thedition.

[0146] 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.

[0147] 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.

[0148] 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.

[0149] 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.

[0150] 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 Alport28yndromem. Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0151] 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.

[0152] 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.

[0153] 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).

[0154] 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.

[0155] 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.

[0156] 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).

[0157] 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.

[0158] 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.

[0159] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1:2011). 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.

[0160] 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).

[0161] 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).

[0162] Brief description of the drawings

[0163] In the following, numerous examples of a medicament containers and injection devices are shown and described in greater detail by making reference to the drawings, in which:

[0164] Fig. 1 schematically illustrates an example of an injection device comprising a medicament container before the medicament container is filled by way of a filling needle,

[0165] Fig. 2 shows the devices according to Fig. 1 when the filling needle penetrates the stopper,

[0166] Fig. 3 illustrates a configuration of the medicament container during fusing or re-sealing of a puncture site of the stopper,

[0167] Fig. 4 shows the device according to Figs. 1-3 before closing a plunger with a closure,

[0168] Fig. 5 shows a final assembly or filling configuration of the medicament container and the injection device,

[0169] Fig. 6 shows a further example of a medicament container with a plunger detached from the stopper,

[0170] Fig. 7 shows a further example of a medicament container, e.g. implemented as a cartridge, Fig. 8 is a flowchart of a method of filling a medicament container as described herein, Fig. 9 shows an example of an aseptic medicament container prepared for filling with a medicament, and

[0171] Fig. 10 is a flowchart of a method of providing an aseptic medicament container in connection with Fig. 9.

[0172] Detailed description

[0173] In Figs. 1-7 there are illustrated numerous examples of a medicament container 10, which in some examples is implemented as an injection device 1. Figs. 1-5 show or illustrate a filling process for filling such a medicament container 10. There, the medicament container 10 is implemented as a pre-filled syringe 4.

[0174] The medicament container 10 comprises an elongated, e.g. cylindrically -shaped barrel 11 with a barrel sidewall 12. The barrel sidewall 12 confines an interior 13 to be filled with a liquid medicament 5. Towards a distal direction 2, the barrel 11 is closed by an outlet 14. The outlet 14 may be provided with an injection needle 6. The injection needle 6 typically comprises a tipped distal end 7. It may be fastened to the outlet 14 of the medicament container 10 by way of a needle mount 8. The needle mount 8 may protrude distally from a distal end 15 of the barrel 11. The entire needle assembly, i.e. the needle mount 8 and the injection needle 6 may be covered by a needle cap 9. This way, the injection needle 7 can be protected against any environmental hazards as well as against any contaminants during shelf-life, retail and shipping. Of course, the needle cap 9 has to be detached from the distal end of the medicament container 10 prior to use the medicament container 10 with or as a syringe 4.

[0175] Towards the proximal direction 3 the barrel 11 is sealed by a movable stopper 20. The stopper 20 comprises a distal side 25 facing towards the distal direction 2 and further comprises a proximal side 26 facing in the opposite proximal direction 3. The stopper 20 is typically made of a thermoplastic elastomeric material. The barrel 11 may be made of a COC-material. The medicament container 10 and hence the pre-filled syringe 4 may be particularly configured for a short-term or long-term storage of the medicament 5 at ultra-low temperatures, e.g. below - 60°C.

[0176] At its proximal end 16 the barrel 11 may be provided with a barrel flange 17 protruding radially outwardly from the longitudinally extending sidewall 12 of the barrel 11. The proximal side 26 of the stopper 20 may be connected, e.g. permanently connected with a plunger 40. The plunger 40 may be made of a plastic material. It may be permanently or at least temporarily and hence detachably connected to the proximal side 26 of the stopper 20. For this, and as shown in Figs. 6 and 7, the distal end of the plunger 40 may be provided with a counter fastening structure 44 complementary shaped or complementary configured to a respective fastening structure 24 at the proximal side 26 of the stopper 20. By way of the fastening structure 24 and the counter fastening structure 44 the plunger 40 may be permanently or at least temporally connected or fixed to the stopper 20 in a tension resistant manner.

[0177] Of course, the distal end of the plunger 40 may abut with the proximal side 26 of the stopper 20 so as to urge the stopper 20 in the distal direction 2 for expelling a dose of the medicament 5 through the outlet 14, e.g. in the course of injecting or dispensing of a dose of the medicament 5.

[0178] As illustrated in Figs. 1 and 2 the barrel flange 17 may be used to immobilize or to fix the barrel 11, and in particular the proximal end 16 of the barrel 11 to a first support structure 34. The first support structure 34 may be provided at a filling site of a pharmaceutical manufacturer. By way of the support structure 34, the barrel 11 can be kept in a well-defined orientation and position. It may be fixed to a base. The support structure 34 comprises an abutment face 35 facing in proximal direction 3 so as to engage with a complementary shaped distally facing abutment face at the barrel flange 17. The abutment face of the barrel flanges 17 may face towards an outside surface of the sidewall 12 of the barrel 11.

[0179] As shown in Figs. 1 and 2, the plunger 40 comprises an elongated plunger rod 43 extending in longitudinal direction (z). The plunger 40 comprises a proximal end 46 opposite to the counter fastening structure 44. At the proximal end 46 the plunger 40 comprises a radially outwardly extending plunger flange 45. The plunger flange 45 may comprise a receptacle 48, e.g. for receiving a closure 50 as will be described below. The plunger 40, in particular the plunger rod 43 comprises a longitudinally extending guiding structure 41. Typically, the guiding structure 41 comprises an elongated hollow channel 42. The hollow channel 42 may extend all along and through the entirety of the plunger rod 43. An insert opening 47 may be provided at or near the proximal end of the plunger rod 43 and hence at the proximal end of the hollow channel 42. The hollow channel 42 may comprise a constant diameter or constant cross-section all along its longitudinal extend.

[0180] The longitudinally extending guiding structure 41 and / or the hollow channel 42 of the plunger 40 may serve to guide a filling needle 30 as shown in Figs. 1 and 2. In an initial position a distal end, e.g. implemented as a tipped and 31 of the filling needle 30, is introduced into the insert opening 47 of the plunger 40 in distal direction 2. It may be advanced in distal direction 2 so as to hit the stopper 20, which is fastened to a distal end of the plunger 40.

[0181] A resulting piercing configuration, in which the distal end of the filling needle 30 penetrates the stopper 20 is shown in Fig. 2. In this configuration and since the filling needle 30 comprises a hollow channel 32 a liquid substance, e.g. a liquid medicament 5 can be filled or inserted into the interior 13 of the medicament container 10. During the filling process and since the interior 13 as initially provided and as shown in Fig. 1 may contain a gaseous medium, the filling needle 30 may comprise at least one or several vent holes or venting channel, e.g. a respective venting structure at or along an outside surface of the filling needle 30, which in the configuration, in which the filling needle 30 pierces the stopper is not closed and remains permeable for excess air to escape from the interior 13 due to ingress or deposition of the medicament 5 in the interior 13 of the medicament container 10.

[0182] As further indicated in Figs. 1 and 2 there may be provided a second support structure 36 to support and / or to immobilize the plunger 40 during or for at least one of the filling process or piercing process. The plunger flange of 45 may comprise radially outwardly extending abutment faces 49, which engage or which abut with complementary shaped proximally facing abutment faces 37 of the second support structure 36. In this way and as illustrated in Figs. 1 and 2 the plunger 40 may get in longitudinal distal abutment with the second support structure 37 while the barrel 11 is or gets in a respective distal engagement or longitudinal engagement with the first support structure 34. In this way the barrel 11 and the plunger 40 can be immobilized relative to each other at least with respect to forces applied in distal direction 2 onto the stopper 20 during insertion of the filling needle 30 into and / or through the stopper 20.

[0183] The illustration of the support structures 34, 36 is only exemplary. The first and second support structures 34, 36 may serve to fix the plunger 40 and / or the stopper 20 relative to the barrel 11 in both longitudinal directions, e.g. in distal direction 2 as well as in proximal direction 3.

[0184] Likewise, there may be provided a third fastening structure 38 and a fourth fastening structures 39 by way of which the barrel 11 and the plunger 40 can be immobilized with regards to force effects acting on the plunger relative to the barrel 11 in proximal direction 3. In this way, also an oppositely directed force effect acting on the plunger or stopper 20 during or for removal of the filling needle 30 from the stopper 20 can be effectively counteracted. In any case and during a movement of the filling needle 30 relative to the stopper 20 it may be beneficial to provide an immobilization of the stopper 20 relative to the barrel 11 in order to maintain a container closure integrity between the stopper 20 and the barrel 11.

[0185] After withdrawal of the filling needle 30 from the stopper 20, e.g. in proximal direction 3, there may remain a puncture site 22 extending through or located in the stopper 20. The puncture site 22 may be impaired with regard to its sealing capability compared to residual portions or parts of the stopper 20 that have not been punctured. Typically, the tipped end 31 of the filling needle 30 has cut through the stopper 20. The stopper 20, typically made of an elastomeric material, may automatically re-seal after withdrawal or retraction of the filling needle 30. However, the puncture site 22 may be prone to ingress of contaminants.

[0186] In order to avoid any negative impact from the puncture site 22 there is provided a fusing or resealing of the puncture site 22 as indicated in Fig. 3. Here, and after filling of the medicament container 10 with the medicament 5 the puncture site 22 of the stopper 20 is fused or re-sealed e.g. by applying a laser beam 28 onto the puncture site 22. Thermal energy deposited by the laser may then fuse or re-seal the puncture site 22.

[0187] The laser beam 28 as well as the filling needle 30 are effectively guided through the hollow channel 42 and / or along the guiding structure 41 of the plunger 40. In this way it can be easily ensured, that the laser beam 22 is directed onto the puncture site 22, which puncture site 22 is defined by that portion on the proximal side 26 of the stopper that has been pierced by the filling needle 30. Hence, by way of the guiding structure 41 and the hollow channel 42 the laser beam 28 can be easily brought in an geometric overlapping configuration with the puncture site 22.

[0188] Thereafter and after sealing the puncture site 22 there may be further provided a closure 50 to close the insert opening 47 of the hollow channel 42 of the plunger 40. The insert opening 47 is provided at a longitudinal proximal end 46 of the plunger 40 plunger rod 42. The insert opening 47 may adjoin into a radially widened receptacle 48 as provided on a proximal side of the plunger flange 45. Typically, an inside diameter or inside cross-section of the receptacle 48 may match or may correspond to a respective outside diameter or outside cross-section of a planarshaped lid portion 51 of the enclosure 50.

[0189] The closure 50, in particular its lid portion 51 comprises an inside surface 53 facing in distal direction 2 when the closure 50 is inserted into the receptacle 48 at the proximal end 46 of the plunger 40. Here, the inside surface 53 may get in direct longitudinal abutment with a bottom of the receptacle 48. The closure 50 may comprise an elongated stem 52 protruding from the inside surface 53. The diameter or outer cross-section of the elongated stem 52 may match or correspond to an inside diameter or inside cross-section of the insert opening 47, which adjoins the receptacle 48.

[0190] Hence, the elongated stem 52 is sized and configured to enter the insert opening 47 of the hollow channel 42. In this way, there can be provided a kind of a self-centering for the closure 50 as seen in radial direction so that the lid portion 51 perfectly fits into the hollow structure of the receptacle 48.

[0191] In a final assembly configuration as shown in Fig. 5, the lid portion 51 may completely fill or occupy the receptacle 48. A proximal side or outside surface 54 of the lid portion 51 or of the closure 50 may flush in transverse direction with the proximal end 46 of the plunger 40 and hence with a proximal end or interface of the sidewall confining the receptacle 48 in circumferential direction.

[0192] As further illustrated in Fig. 6 the method of filling the medicament container and the medicament container as described herein is in no way limited to a pre-filled syringe comprising an injection needle 6 at its distal end. In Fig. 6 the medicament container 10 may be also implemented as a pre-filled syringe 4. But here, the distal end 15 of the barrel 11 may be provided with a different kind of an outlet 14. Here, the outlet 14 comprises a connector 18, e.g. implemented as sa-called Luer connector or as any other standardized connector configured for a fluid-transferring engagement with a complementary shaped counter connector (not shown). This way, the injection device 1 may be connected in a fluid transferring manner, e.g. to an infusion line to infuse a respective dose of the medicament 5 when urging the plunger 40 and hence the stopper 20 in the distal direction 2. The plunger 40 and the stopper 20 are only illustrated as separate parts in Fig. 6. This is only for illustration purpose to visually illustrate the fastening structure 24 and the complementary shaped counter fastening structure 44. The fastening structure 24 and the counter fastening structure 44 may be configured to form a positive junction or positive connection, a non-positive connection or non-positive junction or may form or constitute any other type of a welded and an adhesive connection.

[0193] In some examples the fastening structure 24 and the counter fastening structure 44 may form or constitute a threaded engagement. One of the fastening structure 24 and the counter fastening structure 44 may comprise an outer thread and the other one of the fastening structure 24 and the counter fastening structure 44 comprises a complementary shaped counter-threaded structure in form of an inner thread.

[0194] As further illustrated in Fig. 6 the radial extent or radial width of the plunger 40 may vary compared to the example as shown in connection with Figs. 1-5. In some examples the radial extent of the plunger 40 may be only slightly smaller than a radial extent or radial cross-section of an inside of the sidewall 12 of the barrel 11. In other examples the radial extent of the plunger 40 may be substantially smaller, e.g. it may range between 40-80% of the radial extent or inside diameter of the barrel 11. Depending on the transverse size or radial size of the plunger there may be provided variable force effects between the plunger and the stopper 20. This may have an impact on the deformation of the stopper 20 especially in the radial outside region, where the stopper 20 is in sealing engagement with an inside of the sidewall 12 of the barrel 11.

[0195] In Fig. 7 there is shown another example of a medicament container 10. Here, the medicament container 10 may comprise a cartridge, e.g. a multidose cartridge. There, the outlet 14 at the distal end 15 of the barrel 11 is closed by a pierceable seal 19. The pierceable seal 19 may be fixed to the distal end of the barrel 11 by way of a fastener 56, which may be implemented as a crimped metal cap and which keeps the pierceable seal 19, e.g. made of a rubber or thermoplastic elastomeric material, in place at the distal end 15 of the barrel 11.

[0196] The medicament container 10 as shown in Fig. 7 may comprise multiple doses of the medicament 5. It may be used in connection with a syringe and / or in connection with a pen-type injector.

[0197] New paragraph in Fig. 8 numerous example steps of filling the medicament container 10 are further described by way of a flowchart. Here, and in a first step 100 the medicament container 10 is provided, which is initially sealed by the stopper 20. In a subsequent step 102 the stopper 20 is immobilized relative to the barrel 11. Here, the plunger 40 is fixed to the stopper 20. For immobilizing the stopper there can be provided a fastening or engaging both, the plunger 40 and the barrel 11 to respective externally provided support structures 34, 36. This way and by controlling a position of the plunger 40 relative to the barrel 11 also the position of the stopper 20 relative to the barrel can be controlled and / or fixed.

[0198] In a subsequent step 104 there is introduced the filling needle 13 through the plunger 40 and through the stopper 20. In step 106 the medicament, e.g. in form of a liquid substance, is provided through the filling needle 30 and into the interior 13 of the medicament container 10. Thereafter and in step 108 the filling needle 30 is retracted in proximal direction 3 and is brought into a position outside the stopper 20 and / or outside the plunger 40. In a subsequent step 110 the puncture site 22 formed or constituted by piercing the stopper 20 with the filling needle 30 is fused or re-sealed, e.g. by making use of a laser beam 28.

[0199] In Fig. 9 and 10 a method of providing an aseptic medicament container for filling with a medicament 5 is described. The aseptic medicament container 10 as shown in Fig. 9. is substantially identical to any of the above-described medicament containers 10 in accordance to Figs. 1-7 with the exception that the interior 13 of the medicament container 10 according to Fig. 9 is empty. Here, the aseptic container 10 is provided or assembled by providing a longitudinal barrel 11 with a tubular sidewall 12. The stopper 20 as described above is introduced in longitudinal distal direction 2 into the barrel 11 until it arrives at a predefined longitudinal position. The predefined longitudinal position of the stopper 20 may be defined by the nominal filling volume of the medicament container 10.

[0200] The stopper 20 is inserted into the interior of the barrel 11 so as to provide an empty space and hence an empty interior 13 between the outlet 14 and the stopper 20. By introducing the stopper 20, which may be equally connected with a plunger 40, an outside facing sidewall 21 of the stopper 20 may engage, e.g., sealingly engage with an inside surface of the sidewall 12 of the barrel 11. After introducing and optionally fixing the stopper 20 into and / or inside the barrel 11 there is applied energy into the interior 13 and into the interface 29 between the stopper 20 and the sidewall 12 of the barrel.

[0201] The interface 29 may be a sealing interface between the outside sidewall 21 of the stopper 20 and an inside surface of the sidewall 12 of the barrel 11. By introducing energy into the interface 29 as well as into the interior 13, the interior 13 can be sterilized. By way of energy introduction, e.g. by introducing thermal energy into the interface 29, the sealing capability of the interface 29 can be improved. In some examples energy is deposited or introduced into both, the interface 29 and into the interior 13 by irradiating the medicament container 10 with electromagnetic radiation 60 from outside.

[0202] The electromagnetic radiation 60 may comprise gamma radiation or may substantially consist of gamma radiation. Application of gamma radiation is of particular use to sterilize the interior 13 of the empty medicament container 10. Application of gamma radiation into the interface 29 between an outside sidewall 21 of the stopper 20 and an inside surface of the sidewall 12 of the barrel 11 may significantly improve the container closure integrity.

[0203] This may particularly apply for material combinations of barrel and stopper, where the barrel 11 comprises a cyclic-olefin polymer or copolymer and wherein the stopper 20 comprises a thermoplastic elastomer. Here, there may be provided a kind of a structural bonding or a structural adherence between the mutually engaging surfaces of the stopper 20 and the sidewall 12 of the barrel 11 thereby improving container closure integrity. In this way, the medicament container 10 may become suitable for storage of a medicament at low temperatures, at ultra-low temperatures or even at cryogenic temperatures.

[0204] In Fig. 10 the various method steps of providing the aseptic medicament container 10 as shown in Fig. 9 are indicated. In step 200 there is provided the barrel 11 and the stopper 20. In step 202 the stopper 20 is introduced into the barrel 11, e.g. from the proximal end 16 of the barrel towards the distal end 15. Introduction of the stopper 20 into the barrel 11 is conducted only to a limited extent so as to provide an empty space between the stopper 20 and the distal end 15 of the barrel is 11.

[0205] In step 204 there is applied energy to both, the interior 13 of the barrel 11 and to the interface 29 between the stopper 20 and the sidewall 12 of the barrel 11. Deposition of energy is typically provided by irradiating the medicament container 10 with gamma radiation in step 204. Gamma radiation as applied in step 204 may serve both, sterilizing the interior 13 of the barrel 11 as well as improving the container closure integrity of the interface 29, specifically for storage of the medicament container at low temperatures, ultra-low temperatures or cryogenic temperatures. Reference Numbers

[0206] 1 injection device

[0207] 2 distal direction

[0208] 3 proximal direction

[0209] 4 pre-filled syringe

[0210] 5 medicament

[0211] 6 injection needle

[0212] 7 tipped end

[0213] 8 needle mount

[0214] 9 needle cap

[0215] 10 medicament container

[0216] 11 barrel

[0217] 12 barrel sidewall

[0218] 13 interior

[0219] 14 outlet

[0220] 15 distal end

[0221] 16 proximal end

[0222] 17 barrel flange

[0223] 18 connector

[0224] 19 seal

[0225] 20 stopper

[0226] 21 sidewall

[0227] 22 puncture site

[0228] 24 fastening structure

[0229] 25 distal side

[0230] 26 proximal side

[0231] 28 laser beam

[0232] 29 interface

[0233] 30 filling needle

[0234] 31 tipped end

[0235] 32 channel

[0236] 34 support structure

[0237] 35 abutment face

[0238] 36 support structure

[0239] 37 abutment face

[0240] 38 support structure 39 support structure

[0241] 40 plunger

[0242] 41 guiding structure

[0243] 42 hollow channel 43 plunger rod

[0244] 44 counter fastening structure

[0245] 45 plunger flange

[0246] 46 proximal end

[0247] 47 insert opening 48 receptacle

[0248] 49 abutment face

[0249] 50 closure

[0250] 51 lid portion

[0251] 52 elongated stem 53 inside surface

[0252] 54 outside surface

[0253] 56 fastener

[0254] 60 radiation

Claims

Claims1 . A method of providing an aseptic medicament container (10) for filling with a medicament (5), the method comprising: providing a barrel (11) with a barrel sidewall (12) and comprising an outlet (14) at a distal longitudinal end (15) of the barrel (11), inserting a stopper (20) into the barrel (11) from a longitudinal proximal end (16) of the barrel (11) and positioning the stopper (20) at a predefined longitudinal distance from the outlet (14) of the barrel (11) to confine an interior (13) of the barrel (11), which is to be occupied by the medicament (5) after sterilization, and introducing energy into the interior (13) of the barrel (11) to sterilize the interior (13) of the barrel (11).

2. The method according to claim 1 , further comprising introducing energy into an interface (29) between the stopper (20) and the sidewall (12) to improve a sealing capability of the interface (29).

3. The method according to claim 1 or 2, wherein introducing energy into the interior (13) of the barrel (11) and / or into the interface (29) between the stopper (20) and the sidewall (12) comprises applying electromagnetic radiation (60) into the interior (13) of the barrel (11) and / or into the interface (29) between the stopper (20) and the sidewall (12).

4. The method according to any one of the preceding claims, wherein ionizing radiation is applied into the interior (13) of the barrel (11) and / or into the interface (29) between the stopper (20) and the sidewall (12).

5. The method according to any one of the preceding claims 2 to 4, wherein at least one of an outside facing sidewall (21) of the stopper (20) and an inside facing surface of the sidewall (12) of the barrel (11) is at least one of chemically, mechanically or structurally modified by the introduction of energy into the interface (29) between the stopper (20) and the sidewall (12).

6. The method according to any one of the preceding claims, wherein: after sterilization of the interior (13) the stopper (20) is penetrated by a filling needle (30), and the medicament (5) is introduced into the interior (13) via the filling needle (30).

7. The method according to claim 6, wherein the stopper (20) is at least temporarily immobilized relative to the barrel (11) before and / or during the stopper (20) is punctured by the filling needle (30).

8. The method according to any one of the preceding claims, wherein the stopper (20) comprises a distal side (25) and a proximal side (26), wherein the distal side (25) faces towards the distal longitudinal end (15) of the barrel (11) and wherein the proximal side (26) faces towards the proximal longitudinal end (16) of the barrel (11) and wherein the stopper (20) comprises a fastening structure (24) at the proximal side (26) for fastening to a plunger (40) and wherein the stopper (20) is fastened to the plunger (40) and is at least temporarily immobilized relative to the barrel (11) through the plunger (40).

9. The method according to 8, wherein the plunger (40) comprises a proximal end (46) with an insert opening (47) to receive the filling needle (30) and wherein the insert opening (47) is closed and / or sealed by a closure (50).

10. An aseptic medicament container (10) for filling with a medicament (5), the medicament container (10) comprising: a barrel (11) with a barrel sidewall (12), an outlet (14) at a distal longitudinal end (15) of the barrel (11) and a stopper (20) located inside the barrel (11) at a predefined longitudinal distance from the outlet (14) of the barrel (11) to confine an interior (13) of the barrel (11) and sealing the interior (13) of the barrel (11) towards a proximal longitudinal end (16), wherein the interior (13) of the barrel (11) is sterilized by introducing energy into the interior (13).

11. The medicament container (10) according to claim 10, wherein the interior (13) of the barrel (11) confined by the sidewall (12) of the barrel (11), by the stopper (20) and by the outlet, is sterilized and is empty.

12. The medicament container (10) according to claim 11, wherein a sealing capability of an interface (29) between the stopper (20) and the sidewall (12) is improved by the introduction of energy into the interface (29).

13. The medicament container (10) according to claim 12, wherein at least one of an outside facing sidewall (21) of the stopper (20) and an inside facing surface of the sidewall (12) of thebarrel (11) is at least one of chemically, mechanically or structurally modified by the introduction of energy into the interface (29) between the stopper (20) and the sidewall (12).

14. The medicament container (10) according to any one of the preceding claims 10 to 13, wherein at least one of the interior (13) of the barrel (11) and the interface (29) between the stopper (20) and the sidewall (12) has been subject to introduction of energy through irradiation with electromagnetic radiation (60).

15. The medicament container (10) according to any one of the preceding claims 10 - 14-, wherein the interior (13) of the barrel (11) is filled with a medicament (5), which has been introduced into the barrel (11) via a filling needle (30) penetrating the stopper (20).

16. An injection device (1) for injecting a liquid medicament (5) into biological tissue, the injection device comprising a medicament container (10) according to any one of the preceding claims 10 - 15.

Images