Medicament container for lyophilizable medicament

Abstract

In one aspect the present disclosure relates to a medicament container (10) for a lyophilizable and reconstitutable pharmaceutical product (6, 7), the medicament container (10) comprising: - a flexible bag (11) defining a chamber (12), - the chamber (12) comprising a chamber cavity (13) configured to hold the pharmaceutical product (6, 7), wherein the chamber cavity (13) is confined at least in sections by a chamber wall (18), - wherein the chamber wall (18) comprises a membrane portion (34), which is semipermeable and allows permeation of vapor (9) from the chamber cavity (13) through the membrane portion (34) to an exterior (4) of the chamber (12), and - an outer wrapping (50) entirely enclosing the flexible bag (11).

Description

[0001] Medicament Container for Lyophilizable Medicament

[0002] Description

[0003] Field

[0004] The present disclosure relates to the field of reconstitutable drug formulations, and in particular to medicament containers for lyophilizing and reconstituting a lyophilized medicament. In a further aspect the present disclosure relates to methods of lyophilizing and reconstituting a lyophilized and reconstitutable injectable pharmaceutical product or medicament.

[0005] Background

[0006] Patients suffering from certain diseases like, for example, haemophilia or requiring enzyme replacement therapy have to take regular intravenous (IV) infusions. The infusions often have to be mixed and prepared, sometimes to the specific needs of the patient, (and sometimes a short time before drug administration) which may include reconstitution of the drug powder from multiple vials using an exact amount of sterile liquids like water and / or saline. As this preparation process is typically complex and tedious, it is usually performed by a health care professional in a clinic or pharmacy, potentially using lab equipment.

[0007] Generally, administering a medicament by way of infusion may require a rather clean or sterile environment. A patient may therefore have to regularly visit an ambulance or health care center.

[0008] Self-medication or home-medication for administering a medicament through infusion or injection is and remains quite challenging but is very attractive for patients thereby avoiding problems and circumstances involved in visiting a health care center. With home- or self- medication a patient or user, e.g. intending to establish a vascular access to a patient's body, may be obliged to use only one hand, which might be rather cumbersome and thus challenging.

[0009] In addition, it is often required to establish or maintain a clean and / or sterile environment especially in the field of home-medication or self-medication as well as providing of a clean and sterile storage environment for medicaments and medicament containers, medical device accessory and medical devices.

[0010] Long-term storage stability of liquid medicaments may be achieved by prior lyophilization. Through lyophilization the shelf-life of a pharmaceutical product can be extended and standardized. Lyophilization is the process of removing a liquid portion from a frozen sample by converting the liquid portion directly into vapor without the intermediate formation of the liquid.

[0011] A lyophilized pharmaceutical product requires reconstitution before administration to a patient. Here, a reconstituting liquid, such as a solvent or diluent, e.g. in form of water for injection, is brought in direct contact with the lyophilized pharmaceutical product. The process of reconstitution may be accompanied by a well-defined mechanical treatment, such as a rolling motion, shaking motion or well-defined turning or tumbling. Handling of the pharmaceutical product during both, lyophilization as well as reconstitution, has to be conducted under predefined conditions. Any contaminants that may harm the pharmaceutical product, the lyophilized pharmaceutical product and / or the reconstituting liquid have to be kept away. At the same time overall handling of the pharmaceutical product during both, lyophilization and reconstitution should be simple, intuitive and cost efficient.

[0012] It is therefore desirable to provide improvements to medicament containers for a lyophilizable and reconstitutable pharmaceutical product as well as to the process of lyophilization and reconstitution of the pharmaceutical product.

[0013] Summary

[0014] In one aspect there is provided a medicament container for a lyophilizable and / or reconstitutable pharmaceutical product. The medicament container comprises a flexible bag defining or comprising a chamber. The chamber comprises or defines a chamber cavity. The chamber and hence the reservoir formed by the chamber cavity is configured to hold the pharmaceutical product. The chamber cavity is confined at least in sections by a chamber wall.

[0015] The chamber wall, which at least in sections confines the chamber cavity comprises a membrane portion. The membrane portion of the chamber wall is semipermeable and allows permeation of vapor from the chamber cavity through the membrane portion to an exterior of the chamber.

[0016] By providing the chamber and hence the chamber wall with a membrane portion, the liquid lyophilizable pharmaceutical product may be filled into the chamber cavity, e.g. through an inlet port. Thereafter, the chamber or chamber cavity may be sealed or closed, e.g., by closing the inlet port. The liquid lyophilizable pharmaceutical product located inside the chamber cavity may then undergo a lyophilization process, e.g., by exposing the medicament container in its entirety to respective or predefined lyophilizing conditions, during which a gaseous fraction of the freeze-dried pharmaceutical product may escape or permeate through the membrane portion.

[0017] Insofar, the medicament container is suitable to hold or to store a liquid lyophilizable pharmaceutical product, which may be subject to lyophilization while remaining inside the container cavity. As a result of the lyophilization process the liquid lyophilizable pharmaceutical product may transition into a lyophilized pharmaceutical product, which is reconstitutable, e.g., by mixing or dissolving with a suitable diluent or reconstituting liquid. Hence, the medicament container is configured to contain or to hold the pharmaceutical product inside the container cavity either in a liquid lyophilizable state, in a lyophilized reconstitutable state or in a liquid reconstituted state.

[0018] Insofar, the process of filling the medicament container, namely to fill the chamber with a liquid pharmaceutical product may be provided in a pre-defined, e.g., aseptic filling environment, e.g. with a pharmaceutical manufacturer. Thereafter, the entire medicament container with the liquid lyophilizable pharmaceutical product can be transferred to a freeze-dryer and may undergo a lyophilization process.

[0019] The medicament container may be universally used for lyophilization of the pharmaceutical product, it may be further used for long-term storage and transportation of the lyophilized reconstitutable pharmaceutical product and it may be further used as a mixing chamber for mutually mixing the lyophilized pharmaceutical product and the reconstituting liquid to conduct or to execute the reconstituting process.

[0020] Furthermore, the medicament container may be also used as a delivery device. The medicament container may comprise at least one outlet port by way of which the reconstituted medicament can be provided to an injection or infusion device.

[0021] The medicament container further comprises or is provided with an outer wrapping entirely enclosing the flexible bag. The outer wrapping may provide a further barrier for gaseous and / or or liquid media. By way of the outer wrapping, the permeability of the semipermeable membrane or membrane portion can be compensated or effectively annihilated. By wrapping the entire flexible bag into the outer wrapping a contamination of the chamber and / or of optional inlet or outlet ports of the flexible bag can be effectively prevented. Moreover, and by way of the outer wrapping the container-closure integrity of the medicament container can be improved.

[0022] When wrapped inside the outer wrapping, the flexible bag can be stored over a comparatively long time without deterioration. When wrapped in the gas-tight outer wrapping the flexible bag may be ready for shipment and long-term storage. Shipment and / or long-term storage may be conducted under temperatures that may differ from the temperatures required by the lyophilizing process.

[0023] Generally, the flexible bag of the medicament container allows for a rather easy and durable storage as well as transportation of the pharmaceutical product contained therein. By way of a flexible bag also the reconstitution process may be simplified or facilitated, e.g. by squeezing portions of the flexible bag.

[0024] According to a further example the outer wrapping is tight to at least one of water vapor and oxygen. This way, a limited sealing capability of the membrane portion can be effectively compensated. The lyophilized pharmaceutical product remains inside the chamber of the flexible bag after completion of the lyophilization process. It is highly hygroscopic. Since the membrane portion may be permeable to gaseous substances it is of particular benefit to wrap and / or to seal the entire flexible bag in the outer wrapping, which is tight to at least one of water vapor and oxygen. In this way, ingress of water vapor and / or oxygen, which may be present in the exterior surrounding of the medicament container, is effectively hindered to permeate through the membrane portion into the chamber cavity.

[0025] According to a further example the outer wrapping is tight to liquids and / or to gases or gaseous substances. In this way, the outer wrapping may provide or constitute an outer cavity, in which the flexible bag may be contained. The outer cavity as defined by the outer wrapping may be impenetrable for liquid substances and / or for gaseous substances. In this way, the flexible bag can be hermetically sealed inside the outer wrapping.

[0026] According to a further example the outer wrapping comprises a metal foil or the outer wrapping is made of a metal foil. Metal foils provide excellent barrier properties with regards to permeation of gaseous substances and / or liquid substances.

[0027] According to another example the gas-tight outer wrapping comprises a pliable sheet. The outer wrapping may comprise a plastic foil or the like pliable sheet like material.

[0028] According to another example the gas-tight outer wrapping comprises a metal foil. A metal foil may be beneficial both in terms of protecting the interior of the outer wrapping against electromagnetic radiation, thermal influences as well as against ingress or escapement of any gaseous or other contaminating substances. Hence, a metal foil may exhibit excellent barrier properties both in terms of radiation and any gaseous or liquid material. According to another example the gas-tight outer wrapping is opaque. In some examples the gas-tight outer wrapping may comprise at least a transparent portion, by way of which visual inspection through the gas-tight outer wrapping may be enabled. When the gas-tight outer wrapping is opaque, the interior of the outer wrapping, hence the medicament container wrapped inside the outer wrapping can be effectively protected against electromagnetic radiation.

[0029] In some examples, the gas-tight outer wrapping may be partially transparent or opaque. It may comprise a dyed or colored transparent structure. Coloration may block or prevent transmission of light of a pre-defined spectral range, e.g., highly energetic UV light. Suitable colors for the outer wrapping are yellow, red or brownish colors, effective to block electromagnetic radiation in the UV-spectral range.

[0030] In some examples, plastic foils for outer wrappings may also include UV-blocking agents and be clear, colorless and transparent. Transparency may be desired and beneficial for inspection of the contents for e.g. integrity, leakage, defects, contamination, and the like.

[0031] According to another example the gas-tight outer wrapping comprises a label. The label may be provided as a printed label, or as an electronic label. The gas-tight outer wrapping may thus provide a twofold function. It may provide a substrate for fastening a label to the medicament container or to be directly printed material. Furthermore, the gas-tight outer wrapping may provide an additional barrier for protecting the medicament container against environmental influences.

[0032] According to a further example the outer wrapping comprises a transparent window. The transparent window may provide visual inspection of the content located inside the outer cavity as provided or defined by the outer wrapping. In some examples the outer wrapping may comprise a first sheet of a pliable material and a second sheet of a pliable material. The pliable material of the first sheet and of the second sheet may be the same material. In some examples the material of the first pliable sheet and of the second pliable sheet may be different materials.

[0033] The pliable sheet may comprise an inert medical grade plastic material, such as polyvinyl chloride, polyethylene, polypropylene, or high-density polyethylene. The sheet may comprise a multi-laminate of polymer layers for greater durability, e.g., to resist tearing and puncturing that could be encountered in normal handling. The multi-laminate sheet may comprise layers providing a barrier to gas permeation (e.g. oxygen permeation), or light barrier properties (e.g. high-energy light, such as ultraviolet light).

[0034] The outer wrapping, which may be formed by an overlapping configuration of first and second planar sheets, which are welded or connected along their outer circumference. Here, the first pliable sheet and the second pliable sheet may comprise identical geometries such that the first and second sheet may mutually overlap to form the outer cavity between the first and the second sheet. The sheets may be sealed, welded, glued and / or fused together along their outer overlapping circumference or outer perimeter.

[0035] In some examples at least one sheet of the outer wrapping comprises a transparent foil, which provides a transparent window. In this way, the interior of the outer wrapping, i.e., the flexible bag located inside the outer wrapping, can be visually inspected. The transparent window may be semitransparent. It may be dye-doped by a suitable dye, e.g., by way of which highly energetic electromagnetic radiation, e.g., UV radiation can be blocked to enter the outer cavity as defined by the outer wrapping.

[0036] According to another example the outer wrapping comprises at least one of a predetermined breaking structure and a frangible portion for opening the outer wrapping. The predetermined breaking structure may comprise a notch or groove adjoining or merging into a side portion of the outer wrapping. Is. Here, the notch or groove as provided by the predetermined breaking structure may adjoin a circumferential seam that holds together the first and the second sheet or layer of the outer wrapping. The notch or predetermined breaking structure provides an effective handling of the outer wrapping for opening the same. The predetermined breaking structure may also comprise a structurally weakened structure. It may comprise a region of limited material thickness, which is easy to rupture or to disintegrate for opening of the outer wrapping.

[0037] The medicament container as proposed herein facilitates the process of the lyophilization and allows to combine the filling of the chamber of the flexible bag prior to the lyophilization process. Typically, the filling of the chamber may be completed. Then, the chamber may be sealed appropriately and then the flexible bag may become subject to the lyophilization process, which due to the membrane portion of the chamber wall of the chamber leads to a lyophilization of the pharmaceutical product located inside the chamber or chamber cavity.

[0038] According to a further example the flexible bag comprises a first filling port for filling a liquid and lyophilizable pharmaceutical product into the chamber cavity. The first filling port may be closed by a septum, which may be penetrable by a filling device, such as a filling needle. In this way the liquid lyophilizable pharmaceutical product can be introduced and deposited inside the chamber cavity in liquid form. After withdrawal of the filling device the first filling port may be closed or sealed or even re-sealed.

[0039] Accordingly, the chamber cavity may be sealed with respect to the outer environment or exterior at least with regard to the liquid fraction contained inside the chamber cavity. During a subsequent lyophilization process the gaseous or vaporous portion or fraction of the pharmaceutical product may escape through the membrane portion of the chamber wall thus leaving the lyophilized pharmaceutical product inside the chamber. The membrane portion of the chamber provides the benefit to seal the first filling port after filling the liquid lyophilizable pharmaceutical product into the chamber. Overall handling of the medicament container and its flexible bag during and / or for the reconstitution process can be thus facilitated or simplified.

[0040] According to another example the flexible bag further comprises a second filling port for filling the reconstituting liquid in liquid form into the chamber cavity. Also, the second filling port may be provided with a septum or the like seal that may be penetrated or penetrable by a filling device for filling the reconstituting liquid in liquid form into the chamber cavity.

[0041] In some examples, the second filling port may comprise a standardized connector allowing to establish a fluid transferring connecting with an outlet port of a diluent container. The outlet port of the diluent container may comprise a complementary shaped counter connector, which when connected with the connector of the second inlet port of the flexible bag forms or constitutes a fluid transferring coupling between a cavity of the diluent container and the chamber cavity of the flexible bag. The standardized connector may comprise one of a male and a female connector. The standardized counter connector may comprise another one of a male and a female connector.

[0042] Filling of the chamber by a liquid product, either by the liquid pharmaceutical product before lyophilization and / or by the diluent or reconstituting liquid for reconstitution may be conducted at room temperature or at a storage temperature that may be required for the pharmaceutical product. During or for the respective filling processes the pharmaceutical product and / or the reconstituting liquid are provided in a liquid form. The liquid state of the pharmaceutical product and the liquid state of the reconstituting liquid allows for an easy and straightforward filling of the chamber of the flexible bag, respectively.

[0043] Providing the chamber with a respective first filling port and with a second filling port provides a straightforward and intuitive approach to fill the chamber cavity with the liquid pharmaceutical product prior to lyophilization and to fill the chamber cavity with the reconstituting liquid for the reconstitution process.

[0044] According to another example the flexible bag comprises an outlet port to withdraw or to expel a liquid reconstituted pharmaceutical product from the chamber, typically, after the lyophilized pharmaceutical product has been reconstituted inside the chamber by adding a pre-defined amount of the reconstituting liquid. After transferring a predefined amount of the reconstituting liquid into the chamber, a mutual mixing of the reconstituting liquid and the lyophilized pharmaceutical product can be provided in the chamber cavity.

[0045] By providing an outlet and hence by providing an outlet port in the chamber or chamber cavity the reconstituted pharmaceutical product, i.e. the reconstituted liquid medicament can be withdrawn or expelled through the outlet port. The outlet port may be connected or may be connectable in a fluid transferring manner to an injection device or infusion device. The outlet port may comprise a standardized connector and may be thus connected by a standardized connector with at least one of an injection device or a fluid transferring line, e.g., an infusion line. The injection device or infusion device may comprise a needle or the like piercing device to provide an intravenous or subcutaneous injection or infusion of the medicament into biological tissue of a patient.

[0046] The outlet port may be provided with a standardized connector by way of which the outlet port can be non-releasably or releasably connected to the injection device for withdrawal and / or for expelling the liquid reconstituted pharmaceutical product.

[0047] According to a further example, the flexible bag forming or constituting the chamber may be made of one or several pliable sheets of material. Production of the medicament container may be rather cost-efficient and suitable for a mass-manufacturing.

[0048] In some examples the flexible bag may comprise a first sheet of material and a second sheet of material that are welded together or fixed together in a fluid-tight manner along the outer circumference or perimeter of at least one of the first and second sheets of material.

[0049] The chamber cavity may be effectively confined by an upper sheet of material and a lower sheet of material, which are sealed or welded together along a circumferential seam. Such a medicament container is easy to manufacture in a rather cost-efficient way and allows to produce such medicament containers in a mass-manufacturing process.

[0050] In some examples the material of the medicament container forming or contributing to the chamber is transparent, is at least partially transparent or is in sections transparent. A transparent material or a transparent portion of the chamber allows for a visual inspection of the content of the respective chamber cavity. In this way, the configuration or constitution of the lyophilized pharmaceutical product as well as of the reconstituted liquid pharmaceutical product can be visually inspected before and / or after reconstitution.

[0051] According to another example the chamber cavity is confined by a bottom portion and a lid portion. In some examples the chamber is constituted by the bottom portion and the lid portion, which may be connected or fixed together so as to form or to constitute the chamber and the chamber cavity. The bottom portion and the lid portion may be made of the same material. In some examples the bottom portion and the lid portion may be of different materials. The material of the bottom portion may distinguish from the material of the lid portion by a material thickness and / or by a mechanical stiffness or mechanical rigidity.

[0052] In some examples the bottom portion may comprise a degree of elasticity that is lower than a degree of elasticity of the lid portion. In some examples the lid portion may comprise a flexible sheet. The lid portion may comprise a flexible sheet material, which may adapt or conform to the shape of the bottom portion. In further examples the bottom portion may comprise at least one recess, which may be closed by the lid portion. A recess of the bottom portion closed or covered by the lid portion may form or constitute the chamber cavity.

[0053] According to another example the chamber cavity is confined by the bottom portion and by the lid portion exclusively. Hence, the chamber cavity may be obtained or provided by assembling, connecting or closing a single bottom portion with a single lid portion.

[0054] By establishing or forming the chamber cavity by mutually assembling the bottom portion and the lid portion there can be provided a rather easy and cost-efficient manufacturing of the flexible bag.

[0055] According to a further example the bottom portion comprises or forms a receptacle confining at least a portion of the chamber cavity. The receptacle is covered and / or closed or sealed by the lid portion.

[0056] According to a further example the bottom portion may be self-stable. It may comprise a recessed structure with a chamber bottom and an upwardly protruding sidewall. The bottom portion may be structurally stable and may be flexible to a certain extent. It may be deformable so as to facilitate or to enable a squeezing of the chamber. However, it may always relax into a pre-defined initial shape or configuration.

[0057] The bottom portion and the lid portion may be made of a plastic material or polymeric material. The bottom portion may comprise an increased mechanical stability and / or stiffness compared to the lid portion. The bottom portion may be made of a first material. The lid portion may be made of a second material that differs from the first material. The first and the second materials may be of the same class of materials.

[0058] In some examples the first material and a second material may be the same material.

[0059] In some examples, a wall thickness or material thickness of the bottom portion may be larger than a respective wall thickness or sheet thickness of the lid portion. In this way and by having different material thicknesses, the mechanical stability of the bottom portion may be increased compared to the mechanical stability of the lid portion.

[0060] Both, the bottom portion and the lid portion may comprise a rather planar structure. The planar structure of the bottom portion may correspond to the planar structure of the lid portion. Here, an outer perimeter or circumference of the bottom portion may be connected or may be sealed with an outer perimeter of the lid portion. The planar surfaces or outer perimeters of the lid portion and the bottom portion may be substantially identical.

[0061] According to another example the bottom portion of the medicament container comprises a flange portion. The lid portion comprises a circumferential portion or perimeter section, which is fixed to the flange portion or which forms or constitutes the flange portion. The flange portion may be located at a well-defined vertical distance from a bottom of the receptacle of the bottom portion. In this way, the flange portion may provide an increased contact surface for the lid portion. The lid portion may be fastened, e.g., welded, adhesively attached or bonded to the bottom portion via and / or by the flange portion. The bottom portion may comprise a circumferential flange portion, which may be uninterrupted around the outer perimeter of the bottom portion.

[0062] In some examples the flange portion may be provided with at least one of the first filling port, the second filling port and the outlet port. The respective ports may comprise a tubular member, e.g. in form of a tube that is sandwiched between the flange portion of the bottom portion and the lid portion. The ports may traverse or intersect the interface formed or established between the lid portion and the flange portion of the bottom portion. According to a further example the bottom portion comprises a flat-shaped chamber bottom and a sidewall projecting from a plane of the chamber bottom. An upper end of the sidewall facing away from the flat-shaped chamber bottom is connected with the lid portion or is connectable to the lid portion. By implementing a flat-shaped chamber bottom the receptacle as provided by or in the bottom portion may comprise a planar and / or even-shaped chamber or receptacle. Such a planar or even-shaped chamber bottom is of particular benefit to improve exchange of thermal energy between the chamber cavity and the exterior.

[0063] Typically, the medicament container may be subject to cryogenic or considerably low temperatures during at least one of the lyophilizing process and storage. By placing the medicament container onto a respective cooling shelf or onto a respective cooling structure and by providing an even or flat-shaped chamber bottom, there may be provided a comparatively large mechanical contact between the chamber bottom and a cooling equipment, such as the cooling shelf, by way of which thermal energy may be introduced or exchanged between the chamber cavity and the exterior of the medicament container.

[0064] Moreover, a flat-shaped chamber bottom, which may be dimensionally stable, may be also of particular benefit to provide a stable orientation and positioning of the medicament container, e.g., when placed on a surface.

[0065] Generally, the lid portion may be fastened to the flange portion of the bottom portion, wherein the flange portion is located at a well-defined distance from the respective chamber bottom.

[0066] A vertical distance between the lid portion and the chamber bottom is defined by the respective design and vertical extent of the sidewall, respectively.

[0067] According to some examples the flange portion may be located at a longitudinal or upper end of the sidewall that faces away the bottom portion. According to some examples the flange portion may protrude outwardly from the sidewall and hence away from the chamber cavity. This allows to increase the size of the flange portion to improve mutual fixing or adhering to the lid portion.

[0068] In another example the sidewall may be unitarily or integrally shaped with the chamber bottom. The sidewall and the chamber bottom may be made of one and the same material. They may comprise a molded or extruded plastic material, which is substantially inert to the pharmaceutical product as well as to the reconstituting liquid.

[0069] According to some examples, the bottom portion comprises one of a molded body and an extruded body, which is molded or extruded from a plastic material. The plastic material may be substantially inert to the pharmaceutical product and / or to the reconstituting liquid.

[0070] According to another example the sidewall of the flexible bag comprises a corrugated or polygonal structure in a transverse plane, which transverse plane extends parallel to the chamber bottom. A corrugated or polygonal structure may structurally and / or mechanically stabilize the sidewall and hence the entire flexible bag. The corrugated structure or a polygonal structure, e.g. a hexagonal or octagonal structure of the sidewall protruding upwardly from the chamber bottom, may provide an improved stiffness of the sidewall so as to prevent an uncontrolled collapsing of the sidewall when exposed to mechanical impact or respective forces.

[0071] According to a further example the membrane portion is located in the lid portion, which confines an upper side of the chamber cavity that is opposite to a lower side of the chamber cavity. The lower side of the chamber cavity is confined by the bottom portion. Specifically, the lower side of the chamber cavity may be confined by the chamber bottom, which may be located opposite the membrane portion of the lid portion that overlaps with the receptacle or recess as formed by the bottom portion of the flexible bag or medicament container.

[0072] With the membrane portion located in the lid portion and specifically in a portion that overlaps or covers the recess or receptacle as provided in the bottom portion thereby confining the chamber cavity, it can be provided that the membrane portion is automatically or intrinsically kept at a well-defined distance from the chamber bottom. Insofar, it may be provided that when the chamber is filled with the liquid, to be lyophilized pharmaceutical product to a certain or predefined extent, there remains a gaseous fraction inside the chamber cavity. This way it can be provided that the liquid fraction of the content of the chamber cavity does not get in mechanical contact with the membrane portion.

[0073] In this way, the gaseous fraction, e.g., vapor generated during the lyophilization process may easily escape from the chamber cavity through the semipermeable membrane whereas the frozen fraction of the lyophilizable pharmaceutical product remains inside the chamber cavity.

[0074] The surface dimension of the membrane portion may be almost as large as the surface dimension of the flat-shaped chamber bottom. In this way, the total size of the membrane portion may be maximized to an extent as defined by the chamber bottom and / or by the sidewall. Also, the size and / or geometry of the membrane portion of the lid portion may be maximized and may be as large as defined by the perimeter or circumference of an upper end of the sidewall projecting upwardly from the chamber bottom. In examples, wherein the first sidewall extends upwardly and outwardly, e.g., by a predefined inclination, a surface dimension of a section of the lid portion and / or of the membrane portion covering the chamber cavity may be even larger than the chamber bottom.

[0075] With a comparatively large surface of the membrane portion an escape of vapor and hence a rate of permeation of vapor through the membrane portion can be maximized and a duration of the lyophilization process may be reduced.

[0076] According to another example the lid portion comprises a flexible sheet, which is impenetrable for vapor and liquids. The flexible sheet comprises a through opening, which through opening is covered by a semipermeable membrane. The flexible sheet may comprise a through opening only and exclusively in that region that overlaps with the chamber when the lid portion is duly connected and / or fixed to the bottom portion. Residual parts of the lid portion, which may overlap or which may cover the receptacle of the bottom portion may be impenetrable to both, vapor and liquid. In this way, the reconstituting liquid provided inside the chamber cavity may be subject to freezing during the lyophilization process but may be effectively prevented from permeation or escapement from the chamber cavity.

[0077] The flexible sheet with the through opening covered by the semipermeable membrane may form or constitute the membrane portion of the first chamber wall.

[0078] According to some examples the through opening of the flexible sheet of the lid portion comprises an inner edge, which is entirely covered by the semipermeable membrane. Here, an outside circumference of the semipermeable membrane may be connected, attached and / or fixed to the inner edge of the through opening of the flexible sheet of the lid portion.

[0079] According to a further example the medicament container and in particular the flexible bag comprises a lyophilized pharmaceutical product inside the chamber cavity. The medicament container may therefore provide a drug device combination, which is suitable for preparing a lyophilized pharmaceutical product or substance, for storing the lyophilized pharmaceutical product and for reconstituting the lyophilized pharmaceutical product. Specifically, and since the flexible bag containing the lyophilized pharmaceutical product is entirely enclosed or hermetically sealed by the outer wrapping there can be provided a long-term stable storage for the lyophilized pharmaceutical product, even at room temperature and in environments, which may exhibit a comparatively high degree of ambient humidity.

[0080] In a further aspect the present disclosure also relates to a kit for reconstituting a lyophilized pharmaceutical product. The kit comprises a medicament container as described above, wherein the medicament container comprises a lyophilized pharmaceutical product inside the chamber cavity. The flexible bag of the medicament container further comprises a second filling port for filling the reconstituting liquid in liquid form into the chamber cavity. The kit further comprises a diluent container. The diluent container comprises a flexible diluent bag. The diluent bag defines a diluent chamber. The diluent chamber comprises a diluent chamber cavity, which is filled with the reconstituting liquid, e.g., water for injection.

[0081] The diluent container further comprises a diluent outlet port configured to establish a flow connection with the second filling port of the medicament container. By mutually connecting the diluent outlet port with the first filling port of the medicament container or of the flexible bag and by establishing a respective flow connection or flow communication between the diluent chamber and the chamber cavity of the flexible bag of the medicament container the diluent as initially provided inside the diluent chamber can be transferred into the chamber cavity of the flexible bag of the medicament container.

[0082] In this way there can be provided a mechanical contact between the reconstituting liquid and the lyophilized pharmaceutical substance or product. Since the diluent container comprises a flexible diluent bag and since the medicament container comprises a flexible bag the process of reconstituting can be accompanied by squeezing the respective bags for both, transferring of the reconstituting liquid from the diluent container into the flexible bag of the medicament container and for assisting or providing a well-defined mechanical treatment or mixing of the reconstituting liquid and the lyophilized pharmaceutical product.

[0083] In a further example an amount of the reconstituting liquid inside the diluent chamber cavity matches with an amount of the lyophilized pharmaceutical product inside the chamber cavity in order to reconstitute a predefined amount of the liquid pharmaceutical product. Hence, with the kit for reconstituting the lyophilized pharmaceutical product the content of the diluent container, specifically, the amount of the reconstituting liquid may match with the content of the medicament container, i.e., the amount of the lyophilized pharmaceutical product inside the flexible bag.

[0084] In this way the reconstituting process can be simplified in that an operator or user conducting the reconstitution process transfers the entirety of the reconstituting liquid as provided inside the diluent chamber into the chamber cavity of the flexible bag of the medicament container. The resulting reconstituted pharmaceutical product will then have a correct and pre-defined concentration of an active pharmaceutical ingredient, which may be ready or suitable for administering to a patient, e.g., by way of injection or infusion.

[0085] According to a further example the diluent outlet port of the diluent container comprises a flow restrictor. The flow restrictor may be implemented as a kind of a check valve. The flow restrictor may provide a unidirectional flow of a liquid, namely from the diluent chamber through the diluent outlet port towards and through the second filling port and finally into the chamber cavity of the medicament container. An opposite direction of flow may be effectively prevented or inhibited by the flow restrictor. In this way, it can be provided that the reconstituting liquid that has been transferred from the diluent chamber cavity into the chamber cavity of the flexible bag of the medicament container cannot reenter the diluent chamber cavity.

[0086] Here, the flow restrictor may effectively prevent or impede reentering of a liquid substance from the chamber cavity of the flexible bag of the medicament container towards and into the diluent chamber cavity of the diluent container when the diluent container and the medicament container are duly connected in a fluid coupling way.

[0087] Furthermore, the flow restrictor may also prevent leakage or leaking when opening a frangible seal of the diluent outlet port. Typically, the diluent outlet port may be provided with a standardized connector, e.g. a Luer-type connector. Accordingly, the second filling port of the medicament container may be also provided with a complementary shaped standardized or Luer-type connector. In this way, the connector of the diluent outlet port and the connector of the second filling port can be mutually connected in order to establish a fluid transferring connection between the diluent container and the medicament container to transfer the reconstituting liquid from the diluent container towards and into the medicament container under sterile or aseptic conditions.

[0088] According to a further aspect the present disclosure also relates to a method of preparing a lyophilized pharmaceutical substance. The method comprises the steps of using a flexible bag of a medicament container as described above and filling a liquid and lyophilizable pharmaceutical product into the chamber cavity of the flexible bag. Thereafter the pharmaceutical product is lyophilized in the chamber cavity. Lyophilization requires depositing the flexible bag in a freeze dryer. After completion of the lyophilization process the flexible bag of the medicament container is enclosed in an outer wrapping.

[0089] In other words, the method of preparing the lyophilized pharmaceutical substance may be also regarded or considered as a method of producing or manufacturing the medicament container as described above. Filling of the liquid and lyophilizable pharmaceutical product into the chamber cavity may be provided by making use of a filling device that is to be connected with the first filling port of the flexible bag of which may be operable to penetrate a seal of the first filling port for filling the liquid and lyophilizable pharmaceutical product into the chamber cavity. The filling process may be conducted through a seal of the first filling port, which seal may automatically re-seal after withdrawal of the penetrating filling device, e.g. in form of a tipped cannula. Otherwise, the first filling port may be closed or sealed after filling the liquid and lyophilizable pharmaceutical product into the chamber cavity.

[0090] Thereafter the chamber cavity of the flexible bag is subject to a lyophilization process. During the lyophilization process the liquid pharmaceutical product located inside the chamber cavity is subject to freeze drying. During the process of freeze drying a gaseous fraction that may sublimate or evaporate from the frozen pharmaceutical product may escape or may permeate through the membrane portion of the chamber wall of the chamber of the flexible bag.

[0091] After completion of the lyophilization process the lyophilized pharmaceutical product is provided as a lyophilized dry powder or lyo-cake of the pharmaceutical product inside the chamber cavity. Thereafter and in order to enable a long-term stable storage of the medicament container the flexible bag is enclosed and / or hermetically sealed in the outer wrapping, which provides a barrier that is tight to at least one of water vapor and oxygen.

[0092] The method of preparing the lyophilized pharmaceutical product is typically conducted by a flexible bag as described above and leads to the preparation or manufacturing of a medicament container as described above. Insofar, all features, effects and benefits as described above in connection with the medicament container and the flexible bag equally apply to the method of preparing the lyophilized pharmaceutical product; and vice versa.

[0093] According to another aspect the present disclosure also relates to a method of reconstituting a lyophilized pharmaceutical substance. The method uses a medicament container as described above, wherein the medicament container and hence the flexible bag of the medicament container comprises a lyophilized pharmaceutical product inside the chamber cavity. In a first step the outer wrapping of the medicament container is opened or removed in order to gain access to the flexible bag that contains the lyophilized pharmaceutical product or substance. Thereafter and in a subsequent step a diluent container, which is filled with a reconstituting liquid, is connected with the chamber cavity of the flexible bag in a fluid transferring way. The reconstituting liquid initially provided inside the diluent container is then brought in contact with the lyophilized pharmaceutical product, e.g., through the liquid transferring coupling between the chamber cavity of the flexible bag of the medicament container and the diluent chamber of the diluent container. Typically, the method of reconstituting the pharmaceutical product is to be conducted with a kit for reconstituting a lyophilized pharmaceutical product as described above. Insofar, all features, effects and benefits as described above in connection with the kit as well as described in connection with the medicament container and the diluent container as described above equally apply to the method of reconstituting the lyophilized pharmaceutical substance; and vice versa.

[0094] The receptacle as formed or constituted by the bottom portion of the chamber cavity may comprise a pre-defined shape or cross-section as seen in a transverse plane, e.g., parallel to the plane of the chamber bottom. The cross-section of the chamber cavity may determine the shape of the lyophilized pharmaceutical product.

[0095] According to a further example any one of the first filling port, the second filling port and the outlet port may be provided and may be embedded in an interface between the bottom portion and the lid portion of the flexible bag of the medicament container. The first filling port may be a sealed filling port. It may be hermetically sealed, e.g., by a pierceable septum. In another example, the first filling port may be sealed by a thermoplastic elastomeric material and / or or by an elastomeric material, which may either automatically re-seal or which may be sealed, e.g. by application of laser radiation and / or the like thermal energy deposition.

[0096] The second filling port and / or the outlet port may comprise a standardized connector, e.g. a Luer-type connector. This way, a transfer of a reconstituting liquid into the chamber cavity as well as a transfer of the reconstituted liquid pharmaceutical product out of the chamber cavity and to a drug delivery device may be facilitated. Arranging or fixing the filling ports and / or the outlet port between the bottom portion and the lid portion may be of particular benefit for ease of manufacturing and for integrating the ports into the enclosure of the chamber cavity as formed by the bottom portion and the lid portion.

[0097] Specifically, the outer perimeter of the lid portion may be welded or sealed to the flange portion of the bottom portion. At least one of the first and the second filling port and the outlet port may be easily and rather effectively sealed in the interface between the flange portion of the bottom portion when the outer perimeter or outer circumference of the lid portion is welded or otherwise connected, sealed and / or fixed to the flange portion of the bottom portion. According to a further example the membrane portion and hence the semi-permeable membrane forms a barrier against microbial contamination. It is impenetrable for liquid substances and may be permeated by gaseous substances. The membrane may be made from one of polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE) and the like materials. The membrane may be tightly laminated into or onto a polymer film and may have a predetermined surface area covering at least a part or all of the upper surface of the chamber cavity or of the bottom receptacle.

[0098] In practice, the membrane portion may be provided or formed by any vent material that is water vapor permeable but which provides effective resistance to bacterial penetration. It may comprise sterile papers, woven or non-woven polymeric fabrics, e.g., spun-bonded polyolefin, and porous polymer membranes such as expanded porous PTFE. Best performance will be obtained with venting media that are hydrophobic, as such materials can retain liquid and resist leakage under a wide range of conditions. Additional considerations in selecting materials for use as a venting media include the materials' resistance to water vapor flow versus their effective pore size. Nominal pore sizes in the 0.2 to 3.0 micrometer range will yield performance in bacterial challenge tests that is generally associated with "sterile barrier" media. The smaller the pore size, the more reliable the sterile barrier performance. Also, nominal pores sizes of 0.1 micrometer, or 0.2 or up to 0.3 or more micrometers, are useful. On the other hand, smaller reference pore sizes in a given material will also yield higher resistance to vapor flow, which can affect productivity in lyophilization.

[0099] According to a further example the outlet port of the flexible bag of the medicament container comprises a flow restrictor, e.g. a check valve, which serves to prevent uncontrolled leakage or leaking when opening a frangible closure, which may be initially provided at the outlet port. In this way an uncontrolled leakage of the reconstituted pharmaceutical product from the chamber cavity can be effectively prevented in the course of connecting the outlet port to a drug delivery device or to an infusion line.

[0100] 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. 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.

[0101] The medicament container as described and defined herein is particularly configured to hold or to accommodate a pharmaceutical product inside a container cavity either in a liquid lyophilizable state, in a lyophilized reconstitutable state or in a liquid reconstituted state. The medicament container is particularly suitable for conducting a lyophilization process, for longterm storage of the lyophilized pharmaceutical product and for reconstituting the lyophilized pharmaceutical product.

[0102] 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. 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.

[0103] Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0104] 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.

[0105] 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. 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.

[0106] 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-112600 (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.

[0107] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.

[0108] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0109] 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.

[0110] 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.

[0111] 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).

[0112] 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, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and immunoglobulin single variable domains. Additional examples of antigen-binding antibody fragments are known in the art.

[0113] The term “immunoglobulin single variable domain” (ISV), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain. As such, immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain. The binding site of an immunoglobulin single variable domain is formed by a single heavy chain variable domain (VH domain or VHH domain) or a single light chain variable domain (VL domain). Hence, the antigen binding site of an immunoglobulin single variable domain is formed by no more than three CDRs.

[0114] An immunoglobulin single variable domain (ISV) can be a heavy chain ISV, such as a VH (derived from a conventional four-chain antibody), or VHH (derived from a heavy-chain antibody), including a camelized VH or humanized VHH. For example, the immunoglobulin single variable domain may be a (single) domain antibody, a "dAb" or dAb or a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof. [Note: Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.

[0115] “VHH domains”, also known as VHHs, VHH antibody fragments, and VHH antibodies, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e., of “antibodies devoid of light chains”; Hamers-Casterman et al. 1993 (Nature 363: 446-448). The term “VHH domain” has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VL domains”). For a further description of VHH’s, reference is made to the review article by Muyldermans 2001 (Reviews in Molecular Biotechnology 74: 277-302).

[0116] For the term “dAb’s” and “domain antibody”, reference is for example made to Ward et al. 1989 (Nature 341 : 544), to Holt et al. 2003 (Trends Biotechnol. 21 : 484); as well as to WO 2004 / 068820, WO 2006 / 030220, WO 2006 / 003388. It should also be noted that, although less preferred in the context of the present invention because they are not of mammalian origin, single variable domains can be derived from certain species of shark (for example, the so-called “IgNAR domains”, see for example WO 2005 / 18629).

[0117] 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. 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).

[0118] 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.

[0119] 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.

[0120] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0121] 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).

[0122] 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). Brief description of the drawings

[0123] In the following, some examples of a medicament container and methods of preparing or reconstituting a lyophilized pharmaceutical product will become apparent in greater detail by making reference to the drawings in which:

[0124] Fig. 1 schematically shows a medicament container comprising a flexible bag and an outer wrapping enclosing the flexible bag,

[0125] Fig. 2 shows a cross-section of the flexible bag of the medicament container according to Fig. 1 ,

[0126] Fig. 3 shows the cross-section according to Fig. 2 with the bottom portion and the lid portion of the flexible bag being separated from each other,

[0127] Fig. 4 is an enlarged sectional view of a portion of the lid portion of the medicament container according to Fig. 3,

[0128] Fig. 5 is a schematic illustration of another example of the flexible bag,

[0129] Fig. 6 is a cross-sectional illustration of the flexible bag inside the outer wrapping,

[0130] Fig. 7 is a schematic illustration of a diluent container inside an outer wrapping, Fig. 8 shows a cross-section along a B-B of Fig. 7,

[0131] Fig. 9 is a schematic illustration of a kit including the medicament container and the diluent container, and an optional syringe device for administration to a patient

[0132] Fig. 10 is a flowchart of a method of preparing a lyophilized pharmaceutical product making use of the medicament container,

[0133] Fig. 11 is another flowchart of a method of reconstituting a lyophilized pharmaceutical product by making use of a kit including the medicament container and the diluent container, and

[0134] Fig. 12 shows numerous kits for preparing a medicament prior to injection or infusion.

[0135] Detailed description

[0136] The medicament container as shown in Figs. 1 -6 comprises a kind of a flexible bag 11. The flexible bag 11 comprises a chamber 12. The chamber 12 comprises a chamber cavity 13. The chamber 12 and hence the chamber cavity 13 is confined at least in sections by a chamber wall 18. The chamber 12 is confined at least in sections by a chamber wall 18. In the presently illustrated example the chamber wall 18 may form part or may be implemented as a part of a lid portion 30 closing or covering a receptacle 28 that may coincide or may contribute to the chamber cavity 13. The chamber wall 18 is provided with a membrane portion 34. The membrane portion 34 of the chamber wall 18 and hence of the lid portion 30 is semipermeable and allows permeation of vapor 9 from the chamber cavity 13 through the membrane portion 34 to an exterior 4 of the chamber 12. The vapor 9 may be produced or generated during a lyophilization process, in which a liquid and lyophilizable pharmaceutical product 6 is located inside the chamber cavity 13. The chamber cavity 13 may be effectively closed by the chamber wall 18 such that vapor 9 generated during the lyophilization process is allowed to permeate and / or to escape through the membrane portion 34 into the exterior 4.

[0137] In this way it may be provided that the chamber cavity 13 is sealed or closed in a liquid-tight manner before becoming exposed to a lyophilization process or to lyophilization conditions.

[0138] As it is further apparent from Fig. 1 the chamber 12 and hence the chamber cavity 13 is provided with a first filling port 40 and with a second filling port 42 or inlet port. The first filling port 40 may be sealed by a seal 46. The second inlet port 42 may be provided with a connector 45, e.g., a standardized connector, such as a Luer-type connector for connecting the second filling port 42 with a diluent container 80 as shown in Fig. 7. The filling ports 40, 42, which may be also denoted as inlet ports 40, 42, may be sealed, e.g., by a pierceable septum, e.g., by a rubber septum or by a plastic septum, e.g., made of a thermoplastic elastomer.

[0139] The filling port 40 may be also sealed by welding, heat sealing or high-frequency sealing. Hence the filling port 40 may be void of a pierceable septum. Typically, the first filling port 40 is configured to fill the liquid pharmaceutical product 6 into the chamber cavity 13. This can be provided with a filling device, such as a filling cannula or filling needle under predefined sterile or aseptic conditions.

[0140] The chamber cavity 13 and hence the flexible bag 11 is also provided with an outlet port 44, which may be also provided with a standardized connector 45. By way of the outlet port 44, a fluid transferring line, such as an infusion line or the like injection device 72 may be likewise coupled to the chamber cavity 13. The outlet port 44 as well as the second filling port 42 may be provided with a fluid-transferring coupling or connector 45, such as a Luer-type connector or Luer-type coupling.

[0141] As further illustrated in Fig. 1 , the first and second filling ports 40, 42 may be provided on a common side 14 of the rectangularly shaped flexible bag 11 . The outlet port 44 may be provided on an opposite side 15. The opposite sides 14, 15 may be separated by parallel extending long sides 16, 17 of the flexible bag 11 . Providing of both filling ports 40, 42 on one side 14 and providing the outlet port 44 at an opposite side 15 may be beneficial for an intuitive and failuresafe use of the flexible bag 11 and the medicament container 10.

[0142] The medicament container 10 as shown in Figs. 1-6 is typically assembled or is made of two main parts, namely a bottom portion 20 and a lid portion 30. The bottom portion 20 is shown in Fig. 3 separate from the lid portion 30. The lid portion 30 may comprise a flexible sheet 39, which may adapt to the shape of the bottom portion 20. The bottom portion 20 may comprise a plastic material. Also, the bottom portion 20 may be deformable or may be elastic to a certain degree so as to facilitate or to enable a mixing of the liquid or lyophilized substance located inside the chamber cavity 13 through external mechanical impact.

[0143] However, the bottom portion 20 may comprise a self-stable structure as shown in Fig. 3. Specifically, the bottom portion 20 may comprise a rather planar-shaped outer bottom structure 21 comprising or defining a planar-shaped chamber bottom 22. The chamber bottom 22 may adjoin a protruding sidewall 23.

[0144] Such a planar-shaped bottom structure 21 and the planar chamber 22 are of particular use or benefit when positioning the medicament container 10 onto a shelf structure 5 during the lyophilization process as indicated in Fig. 2. The shelf structure 5 may be provided at a predefined temperature and may thus serve to transfer thermal energy into or out of the chamber cavity.

[0145] The sidewall 23 may be integrally formed with the chamber bottom 22. The chamber bottom 22 and the sidewall 23 may form a receptacle 28 being open towards the top. As shown in Fig. 3, the portion of the first sidewall 23.

[0146] As it is further apparent from Fig. 3 the lid portion 30 comprises a circumferential section 32 that matches with a respective circumference of the bottom portion 20. Here, at an upper end of the sidewall 23 is provided an outwardly extending flange portion 26 that provides a respective support for the lid portion 30. The lid portion 30 may be fastened to the bottom portion 20 via the flange portion 26 and the circumferential section 32 fastened or fixed to the flange portion 26.

[0147] The circumferential section 32 and hence the outer perimeter of the lid portion 30 may be welded or sealed to the flange portion 26. The lid portion 30 may comprise a planar flexible sheet 39 that entirely covers the open receptacle 28. In this way, the chamber cavity 13 can be sealed against the exterior 4. The outwardly extending flange portion 26 may be also beneficial to enhance mechanical stability of the bottom portion 20. The outwardly extending flange portion 26 may be integrally formed with the adjoining sidewall 23. The bottom portion 20 may comprises a mechanically stable yet flexible structure. The bottom portion 20 may comprise a molded or deep-drawn body. The material strength or material thickness of the bottom portion 20 may be larger than a material strength or material thickness of the lid portion 30.

[0148] In the example as shown in Fig. 5 the sidewall 23 comprises a corrugated or polygonal structure 24. In the illustrated example the sidewall 23 comprises a star-shaped or hexagonal structure as seen in a plane transverse to the extent of the sidewall 23. The polygonal structure 24 may enhance mechanical stability of the bottom portion 20 and may be effective to prevent a collapsing of the sidewall 23. In this way, the bottom portion 20 can be implemented as a selfstable structure providing a receptacle 28 which is open towards the top and which is confined upwardly by the laterally extending flange portion 26. The receptacle 28 may be covered by the lid portion 30, specifically by the membrane portion 34 of the lid portion 30 to allow permeation of vapor 9 through the semi-permeable membrane 38 of the membrane portion 34 during the lyophilization process.

[0149] At least a section or portion of the lid portion 30 that overlaps with the receptacle 28 is provided with the membrane portion 34. As becomes further apparent from the enlarged cross section according to Fig. 4 the membrane portion 34 comprises a through opening 37 extending through the flexible sheet 39 of the lid portion 30. The lid portion 30 comprises an outer layer 31 and an inner layer 33. At least one of the layers 31 , 33 is impenetrable for gaseous substances as well as for liquid substances. Along an inside edge 35 of the through opening 37 extending through the outer layer 31 and the inner layer 33 there is fixed a membrane 37 between the outer layer 31 and the inner layer 33. Here, the membrane 38 may be attached or welded to the multilayered sheet of the lid portion 30. The membrane 38 entirely covers the through opening 37 formed in the lid portion 30. In this way, the membrane portion 34 is provided with a semipermeable membrane 38 which allows permeation of vapor 9 from the chamber cavity 13 during the lyophilization process.

[0150] In this way, the medicament container 10 can be used for both, a lyophilization process as well as for a reconstituting process after long-term storage and after lyophilization of the pharmaceutical product 6.

[0151] As further illustrated in Figs. 1 and 6 the flexible bag 11 may be wrapped in an outer wrapping 50 thus forming or completing the medicament container 10. The outer wrapping 50 may comprise a first sheet 51 and a second sheet 52. The two sheets 51 , 52 may be folded, welded or adhesively attached together along a circumferential flange 56 or seam thereby forming an outer cavity 55 that is sized to receive the entirety of the flexible bag 11 therein. The sheets 51 , 52 that may constitute the wrapping 50 are impenetrable to gaseous substances and / or liquid substances.

[0152] At least one of the sheets 51 , 52 or at least a portion thereof may comprise a transparent window 59 through which the interior of the outer cavity 55 can be inspected from outside the outer wrapping 50.

[0153] Insofar, the semipermeable membrane 38 and the membrane portion 34 provided in the chamber wall 18 of the chamber 12 of the flexible bag 11 can be effectively sealed against ingress or escape of gaseous substances during transportation and storage of the medicament container 10. Furthermore, the outer wrapping 50 may provide a substrate for attaching a label 54. Insofar, the outer wrapping 50 and the medicament container 10 provided therein may form or constitute a packaging 60 that is provided with a visual or machine-readable label 54. The label 54 may be also provided on an outside surface of at least one of the flexible sheets 51 , 52 outside the flange 56.

[0154] In some examples the label 54 comprises or includes dedicated information regarding the lyophilized pharmaceutical product 7 or the reconstituting liquid 8, such as a product name, batch number, expiration date, the information may be provided in form of a barcode or data matrix code or some other kind of a machine-readable code.

[0155] In Figs. 7 and 8 there is illustrated a separate diluent container 18. The diluent container 80 comprises a flexible bag 81 . The flexible bag 81 comprises or defines a diluent chamber 82 that comprises or defines a diluent chamber cavity 83, which is filled with a reconstituting liquid eight. The reconstituting liquid eight may comprise water for injection or other solvents to provide reconstitution of the lyophilized pharmaceutical product 7.

[0156] The flexible diluent bag 81 comprises a first flexible sheet 84 and a second flexible sheet 85, which may be welded or sealed along their outer perimeter or so compared end. This way there is formed a circumferential flange portion 86. In general, the overall structure of the flexible diluent bag 80 one may resemble or may be substantially equivalent or even identical to the structure of the flexible bag 11.

[0157] As further illustrated in Figs. 7 and 8 the diluent container 80 comprises a diluent outlet port 92, which is configured to establish a flow connection with the second filling port 42 of the medicament container 10 or flexible bag 11 . The diluent outlet port 92 comprises a standardized connector 93. Moreover, the diluent outlet port 92 may comprise a flow restrictor 94. The flow restrictor 94 may comprise a check valve or the like flow restricting member by way of which an uncontrolled leakage of the diluent 8 may be effectively prevented in the course of establishing a flow connection between the diluent chamber cavity 83 and the chamber cavity 13.

[0158] Optionally, the diluent container 80 may comprise a filling port 90 by way of which the reconstituting liquid 8 can be introduced into the diluent chamber cavity 83. The filling port may be an open tube to allow access for a filling needle of the filling machine. After filling, the open tube can be welded, heat sealed or HF-sealed. In a further example, the filling port 90 may be provided with a re-sealable seal 91 . The seal 91 may comprise a pierceable septum that may be penetrated by a filling device, such as a filling cannula. In other examples the seal 91 may be heat-sealed or may be welded after filling of the diluent chamber cavity 83 with the reconstituting liquid 8.

[0159] The diluent container 80 may be also wrapped in an outer wrapping 50' as indicated in Fig. 8. The outer wrapping 50' may comprise the same structure a configuration as the outer wrapping 50 as described above in connection with the medicament container 10. Here, the outer wrapping 50' may form or constitute a packaging 60' and may provide a gas-tight and / or liquid- tight enclosure for the diluent container 80.

[0160] In some examples, at least one of the ports 40, 42, 44, 90, 92 comprises a connector 45, 93 of male type and at least one of the further ports 40, 42, 44, 90, 92 comprises a connector 45, 93 of female type, which female connector is complementary shaped to the male connector. By way of example, the diluent outlet port 92 may have a male type connector 93 that fits to a female type connector 45 provided at the second filling port 42 of the flexible bag 11. The outlet port 44 of the flexible bag 11 may comprise a male-type connector 45 design which is incompatible to the male type connector 45 of the diluent outlet port 92. Rather, the male type connector 45 of the outlet port 44 may be connectable to a complementary shaped female type connector 74 of a drug delivery device 72, such as an injection device. In this way misuse of the medicament container and an undue connection between the flexible bag, the diluent bag and the drug delivery device can be effectively prevented. The female-type connector and the maletype connector may comprise respective female and male Luer type connectors. In another example, the Luer type connectors may be Luer-Lock connectors to provide a more secure fluid connection and to prevent unwanted disconnection. In Fig. 9 there is illustrated a kit 70 comprising a flexible bag 11 comprising the lyophilized pharmaceutical product 7 inside the chamber cavity 13. The kit 70 further comprises a diluent container 80 and hence a diluent bag 81 . Here, the diluent outlet port 92 is connected with the second filling port 42 in a liquid transferring manner. Accordingly, the reconstituting liquid 8 initially provided inside the diluent chamber cavity 83 can be transferred into the chamber cavity 13, where the lyophilized pharmaceutical product 7 can be reconstituted accordingly. The reconstitution process may be accompanied by a well-defined or prescribed squeezing, shaking or some other kind of movement to dissolve the lyophilized pharmaceutical product 7 and to reconstitute the injectable pharmaceutical product 6. s

[0161] Here, the flow restrictor 94 provided in the diluent outlet port 92 effectively prevents a reflux or re-entering of a liquid fraction into the diluent chamber cavity 83.

[0162] After completion of the reconstitution process the outlet port 44 of the flexible bag 11 may be connected in a fluid transferring manner with a drug delivery device 72 as illustrated in Fig. 9. Here, and by way of example the drug delivery device 72 comprises a syringe 73. The syringe 23 comprises a connector 74, complementary shaped to the connector 45 of the outlet port 44. The connector 74 can be connected to the connector 45 in a fluid transferring manner. At least one of the connector 45 and the outlet port 44 of the flexible bag 11 may be also provided with a flow restrictor in order to prevent uncontrolled leakage of the reconstituted pharmaceutical product 6.

[0163] The syringe 73 may comprise a tubular-shaped barrel 75 and a movable plunger 76 inside the barrel 75. By moving the plunger 76 in proximal direction, i.e., in a direction facing away from the connector 74, the reconstituted liquid pharmaceutical product 6 can be transferred into the cavity of the barrel 74.

[0164] Providing a kit 70 as shown in Fig. 9 is of particular benefit in that the total amount of lyophilized pharmaceutical product 7 as provided inside the chamber cavity 13 may exactly match with the amount of the reconstituting liquid 8 as provided in the diluent chamber 83. By connecting the diluent chamber 83 and the chamber cavity 13 and by transferring the entirety of the reconstituting liquid 8 into the chamber cavity 13, the reconstituting liquid 8 and lyophilized pharmaceutical product 7 can be mixed, thus leading to a well-defined concentration of the reconstituted liquid pharmaceutical product 6.

[0165] In the further illustration according to Fig. 12 there may be provided numerous kits 70, 70' 70" each of which comprising a diluent container 80, 80', 80" and a flexible bag 10, 10', 10", which are provided with a well-defined amount of a reconstituting liquid 8 and a matching amount of a lyophilized pharmaceutical product 7. As shown in Fig. 12 a drug delivery device 72 can be individually and / or sequentially connected to the outlet port 44 of the various flexible bags 10, 10', 10" after conducting respective reconstitution processes. In this way, there can be provided a cumulative drug product transfer from multiple kits 70, 70', 70" and hence from multiple flexible bags and 10, 10', 10" to a drug delivery device 72.

[0166] In the flowchart of Fig. 10 the method of preparing a lyophilized pharmaceutical product 7 is schematically illustrated. Here, in a first step 100 an empty flexible bag 11 as described herein is used. In step 102 a liquid lyophilizable pharmaceutical product 6 is inserted or filled into the chamber cavity 13, e.g. through the first filling port 40, and the port is sealed. Thereafter and in step 104 the flexible bag 11 filled with the liquid pharmaceutical product undergoes a lyophilization process. Upon completion of the lyophilization process the lyophilizable pharmaceutical product 6 has been converted into a lyophilized pharmaceutical product 7 as indicated in Fig. 6. The lyophilized pharmaceutical product 7 may be provided as a powdered or cake-like substance.

[0167] After completion of the lyophilization process the flexible bag 11 is wrapped in the outer wrapping 50 in step 106. The flexible bag 11 is then configured and prepared for a long-term storage or transportation at suitable temperatures. After completion of the lyophilization process and after wrapping of the flexible bag 11 in the outer wrapping 50 the so-formed medicament container 10 may be exposed to room temperature or to predefined storage temperature.

[0168] In Fig. 11 there is shown a flowchart of reconstituting a lyophilized pharmaceutical product 7 as provided in the medicament container 10. Here, the lyophilized pharmaceutical substance 7 is provided inside the chamber cavity 13. The reconstituting liquid 8 is provided by and inside a separate diluent container 80.

[0169] In step 200, the medicament container 10 as described above is used. In a subsequent step 202 the outer wrapping 50 is opened, e.g. by making use of the predefined breaking structure 57 or frangible portion 58. Accordingly, and upon opening or removing of the outer wrapping 50, the flexible bag 10 or at least two of its ports 42, 44 become accessible from outside.

[0170] In step 204 the diluent outlet port 92 is connected to the second filling port 42 and the entirety of the reconstituting liquid 8 as provided inside the diluent chamber cavity 83 is transferred into the chamber cavity 13. Subsequently and in step 206 at least a portion or the entirety of the lyophilized pharmaceutical product 7 is dissolved and / or reconstituted. In step 206 the reconstitution process may be conducted, e.g. by applying a predefined motion to or into the flexible bag 11 . The liquid 8 and the pharmaceutical substance 6 may be mixed by applying well-defined shaping, tumbling, turning, twisting, squeezing or rolling motion to the medicament container 10. Thereafter, the reconstituted pharmaceutical product may be ready for administering into biological tissue and the chamber cavity 13 may be connected to a drug delivery device 72 via the outlet port 44.

[0171] Reference Numbers

[0172] 4 exterior

[0173] 5 shelf structure

[0174] 6 liquid pharmaceutical product

[0175] 7 lyophilized pharmaceutical product

[0176] 8 reconstituting liquid

[0177] 9 vapor

[0178] 10 medicament container

[0179] 11 flexible bag

[0180] 12 chamber

[0181] 13 chamber cavity

[0182] 14 side portion

[0183] 15 side portion

[0184] 16 side portion

[0185] 17 side portion

[0186] 18 chamber wall

[0187] 20 bottom portion

[0188] 21 outer bottom

[0189] 22 chamber bottom

[0190] 23 sidewall

[0191] 24 polygonal structure

[0192] 26 flange portion

[0193] 28 receptacle

[0194] 30 lid portion

[0195] 31 outer layer

[0196] 32 circumferential section

[0197] 33 inner layer

[0198] 34 membrane portion

[0199] 35 edge

[0200] 37 through opening

[0201] 38 membrane

[0202] 39 flexible sheet

[0203] 40 port

[0204] 42 port

[0205] 44 port

[0206] 45 connector 46 seal

[0207] 50 wrapping

[0208] 51 sheet

[0209] 52 sheet

[0210] 54 label

[0211] 55 cavity

[0212] 56 flange

[0213] 57 breaking structure

[0214] 58 frangible portion

[0215] 59 window

[0216] 60 packaging

[0217] 70 kit

[0218] 72 drug delivery device

[0219] 73 syringe

[0220] 74 connector

[0221] 75 barrel

[0222] 76 plunger

[0223] 80 diluent container

[0224] 81 flexible bag

[0225] 82 chamber

[0226] 83 chamber cavity

[0227] 84 flexible sheet

[0228] 85 flexible sheet

[0229] 86 flange portion

[0230] 90 port

[0231] 91 seal

[0232] 92 port

[0233] 93 connector

[0234] 94 flow restrictor

Claims

Claims1 . A medicament container (10) for a lyophilizable and / or reconstitutable pharmaceutical product (6, 7), the medicament container (10) comprising: a flexible bag (11) defining a chamber (12), the chamber (12) comprising a chamber cavity (13) configured to hold the pharmaceutical product (6, 7), wherein the chamber cavity (13) is confined at least in sections by a chamber wall (18), wherein the chamber wall (18) comprises a membrane portion (34), which is semipermeable and allows permeation of vapor (9) from the chamber cavity (13) through the membrane portion (34) to an exterior (4) of the chamber (12), and an outer wrapping (50) entirely enclosing the flexible bag (11).

2. The medicament container (10) according to claim 1 , wherein the outer wrapping (50) comprises at least one sheet (51 , 52) of a pliable material confining an outer cavity (55) inside which the flexible bag (11) is hermetically sealed.

3. The medicament container (10) according to any one of the preceding claims, wherein the outer wrapping (50) is tight to at least one of water vapor and oxygen.

4. The medicament container (10) according to any one of the preceding claims, wherein the outer wrapping (50) is opaque.

5. The medicament container (10) according to any one of the preceding claims, wherein the outer wrapping comprises a transparent window (59).

6. The medicament container (10) according to any one of the preceding claims, wherein the flexible bag (11) comprises a first filling port (40) for filling a liquid and lyophilizable pharmaceutical product (6) into the chamber cavity (13).

7. The medicament container (10) according to any one of the preceding claims, wherein the flexible bag (11) comprises a second filling port (42) for filling the reconstituting liquid (8) in liquid form into the chamber cavity (13).

8. The medicament container (10) according to any one of the preceding claims, wherein the flexible bag (11) comprises an outlet port (44) to withdraw or to expel a liquid reconstituted pharmaceutical product (6') from the chamber (12).

9. The medicament container (10) according to any one of the preceding claims, wherein the chamber cavity (13) is confined by a bottom portion (20) and a lid portion (30).

10. The medicament container (10) according to claim 98, wherein the bottom portion (20) comprises or forms a receptacle (28) confining at least a portion of the chamber cavity (13) and wherein the receptacle (28) is covered and / or closed by the lid portion (30).11 . The medicament container (10) according to claim 10, wherein the bottom portion (20) comprises a flat-shaped chamber bottom (22) and a sidewall (23) projecting from a plane of the chamber bottom (22), wherein an upper end of the sidewall (23) facing away from the flatshaped chamber bottom (22) is connected with the lid portion (30).

12. The medicament container (10) according to claim 11 , wherein the sidewall (23) comprises a corrugated or polygonal structure (24) as seen in a transverse plane, which transverse plane extends parallel to the chamber bottom (22).

13. The medicament container (10) according to claim 11 or 12, wherein the sidewall (23) is unitarily or integrally shaped with the chamber bottom (22).

14. The medicament container (10) according to claim 13, wherein the sidewall (23) and the chamber bottom (22) comprise a molded or extruded plastic material.

15. The medicament container (10) according to any one of the preceding claims 9-14, wherein the bottom portion (20) comprises a flange portion (26) and wherein the lid portion (30) comprises a circumferential portion or perimeter section, which is fixed to the flange portion (26).

16. The medicament container (10) according to any one of the preceding claims 9 to 15, wherein the lid portion (30) comprises a flexible sheet (39), which is impenetrable for vapor (9) and liquids and comprises a through opening (37), which through opening (37) is covered by a semipermeable membrane (38).

17. The medicament container (10) according to any one of the preceding claims, further comprising a lyophilized pharmaceutical product (7) inside the chamber cavity (13).

18. A kit (70) for reconstituting a lyophilized pharmaceutical product (7), the kit (70) comprising: a medicament container (10) according to claim 12, wherein the flexible bag (11) comprises a second filling port (42) for filling the reconstituting liquid (8) in liquid form into the chamber cavity (13), and a diluent container (80) comprising a flexible diluent bag (81) defining a diluent chamber (82), the diluent chamber (82) comprising a diluent chamber cavity (83) filled with the reconstituting liquid (8), and wherein the diluent container (80) further comprises a diluent outlet port (92) configured to establish a flow connection with the second filling port (42) of the medicament container (10).

19. A method of preparing a lyophilized pharmaceutical substance (7) comprising the steps of: using a medicament container (10) according to any one of the preceding claims, 1 to 17 filling a liquid and lyophilizable pharmaceutical product (6) into the chamber cavity (13), lyophilizing the pharmaceutical product (6) in the chamber cavity (13) and enclosing the flexible bag (11) of the medicament container (10) in an outer wrapping (50).

20. A method of reconstituting a lyophilized pharmaceutical substance (7) comprising the steps of: using a medicament container (10) according to claim 17, opening or removing the outer wrapping (50), connecting a diluent container (80), which is filled with a reconstituting liquid (8), with the chamber cavity (13) in a fluid transferring way and bringing the reconstituting liquid (8) in contact with the lyophilized pharmaceutical substance (7).

Images