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WO2025222101A1 - Kit de reconstitution pour la préparation d'un médicament liquide injectable, système de préparation d'un médicament liquide injectable, méthodes de préparation d'un médicament liquide injectable - Google Patents

Kit de reconstitution pour la préparation d'un médicament liquide injectable, système de préparation d'un médicament liquide injectable, méthodes de préparation d'un médicament liquide injectable

Info

Publication number
WO2025222101A1
WO2025222101A1 PCT/US2025/025336 US2025025336W WO2025222101A1 WO 2025222101 A1 WO2025222101 A1 WO 2025222101A1 US 2025025336 W US2025025336 W US 2025025336W WO 2025222101 A1 WO2025222101 A1 WO 2025222101A1
Authority
WO
WIPO (PCT)
Prior art keywords
syringe
section
reconstitution
diluent
syringes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/025336
Other languages
English (en)
Inventor
Stefan Alt
Daniel Auernhammer
René KEMPE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Genzyme Corp
Original Assignee
Genzyme Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genzyme Corp filed Critical Genzyme Corp
Publication of WO2025222101A1 publication Critical patent/WO2025222101A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/002—Compounding apparatus specially for enteral or parenteral nutritive solutions

Definitions

  • Reconstitution kit for preparing an injectable liquid medicament system for preparing an injectable liquid medicament, methods of preparing an injectable liquid medicament
  • the present disclosure relates to a reconstitution kit for preparing an injectable liquid medicament.
  • the present disclosure relates to a system for preparing an injectable liquid medicament and to methods of preparing an injectable liquid medicament
  • IV infusions Patients suffering from certain diseases like, for example, hemophilia or requiring enzyme replacement therapy have to take regular intravenous (IV) infusions.
  • IV 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a reconstitution kit for preparing an injectable liquid medicament.
  • the reconstitution kit comprises a number of syringes comprising at least a first syringe and a second syringe.
  • Each syringe comprises a syringe body, e.g. a barrel, defining a chamber containing a lyophilized and/or reconstitutable pharmaceutical product.
  • the syringe comprises a discharge end, wherein the discharge end comprises a fastening structure and an orifice.
  • a plunger is slidably received within the syringe body to transfer a liquid into and from the chamber through the orifice upon movement of the plunger.
  • the reconstitution kit further comprises a merging adapter.
  • the merging adapter comprises a fluid line, wherein the fluid line comprises a number of sections, wherein the number of sections are interconnected in a fluid conducting manner.
  • the number of sections comprises a number of syringe sections, e.g., at least two syringe sections, for connecting the number of syringes.
  • the number of syringe sections comprise at least a first syringe section and a second syringe section.
  • the first syringe section is connectable to the orifice of the first syringe in a fluid conducting manner, wherein the first syringe section comprises a first counter fastening structure complementary shaped to the fastening structure of the first syringe.
  • the second syringe section is connectable to the orifice of the second syringe in a fluid conducting manner, wherein the second syringe section comprises a second counter fastening structure, wherein the second syringe section complementary shaped to the fastening structure of the second syringe.
  • the number of sections further comprises a diluent feed section, wherein the diluent feed section is connectable to a diluent container in a fluid conducting manner.
  • Lyophilized and/or reconstitutable pharmaceutical products may be reconstituted before administration with a reconstituting liquid, such as a solvent or diluent, e.g. in form of water for injection or saline, to obtain an injectable liquid medicament.
  • a reconstituting liquid such as a solvent or diluent, e.g. in form of water for injection or saline
  • the lyophilized and/or reconstitutable pharmaceutical product is brought in contact with the reconstituting liquid.
  • the lyophilized and/or reconstitutable pharmaceutical product is dissolved, e.g. reconstituted, and an injectable liquid medicament is obtained.
  • the dissolving/reconstitution process can be accelerated or enhanced by gently shaking or gently rolling of the container containing the lyophilized and/or reconstitutable of pharmaceutical product and the liquid diluent.
  • Making use of a syringe containing a lyophilized and/or reconstitutable pharmaceutical product may facilitate exact dosing of the reconstituting liquid used, may facilitate handling and mixing and may allow complete expulsion of the injectable liquid medicament.
  • Making use of the reconstitution kit preparing of an injectable liquid medicament may be facilitated and/or accelerated.
  • the number of syringes containing lyophilized/reconstitutable pharmaceutical product may be simultaneously filled with a reconstituting liquid by connecting the number of syringes and a diluent container to the merging adapter. This way, the chambers of the number of syringes are in fluid connection to one another via the fluid line of the merging adapter and in fluid connection with the diluent feed section and thus with the diluent container.
  • This concept allows a fluid flow from the diluent container that is a connected to the diluent feed section into the chambers of the number of syringes, e.g., by drawing the liquid from the diluent container into the chambers by movement of the plungers.
  • the merging adapter allows to generate an exchange flow between the chambers of at least two of the number of syringes. By this, mixing of the injectable liquid medicament contained in the respective chamber after reconstitution of the respective lyophilized/reconstitutable pharmaceutical product contained in the respective chamber is allowed. Furthermore, by generating an exchange flow between the chambers of at least two of the number of syringes the dissolving process may be enhanced and/or accelerated.
  • the reconstitution kit may provide an individual dose of a pharmaceutical product or a mix of pharmaceutical products in lyophilized/reconstitutable form contained in the number of syringes.
  • different lyophilized/reconstitutable pharmaceutical products or identical lyophilized/reconstitutable pharmaceutical products may be contained in the syringes.
  • the syringes may contain a predefined dose of a lyophilized/reconstitutable pharmaceutical each.
  • the lyophilized/reconstitutable pharmaceutical products may need to be reconstituted by a reconstituting liquid before administration.
  • a person e.g., the patient, may connect the number of syringes to the number of syringe sections of the fluid line of the merging adapter. Further, the person may connect a diluent container, which contained the reconstituting liquid, to the diluent feed section. Afterwards, the chamber of each syringe may be filled with the reconstituting liquid from the diluent container by moving the plunger of the respective syringe. This way, the lyophilized/reconstitutable pharmaceutical product contained in each syringe is brought in contact with the liquid.
  • the lyophilized/reconstitutable pharmaceutical product contained in each syringe will then start to dissolve in the reconstituting liquid.
  • the dissolving/reconstitution process may be enhanced by shaking and rolling the respective syringe and/or by providing an exchange flow between at least two syringes.
  • the injectable liquid medicament contained in each syringe may transferred back into the diluent container or into a medicament container that is connected to the fluid line of the merging adapter in a fluid conducting manner by moving the plungers of the number of syringes.
  • Liquid may be drawn into the respective syringe by moving the plunger in a first direction and may be expelled from the respective syringe by moving the plunger in a second direction opposite to the first direction.
  • an exact volume of a liquid that is drawn into the syringe may be achieved in an easy manner.
  • reconstituting the medicament contained in the chamber with an exact volume of a diluent that is required to obtain the intended concentration for the amount of lyophilized and/or reconstitutable pharmaceutical product contained in the syringe may be facilitated.
  • the exact volume of liquid may be drawn into the syringe by moving the plunger relative to the syringe barrel appropriately.
  • an exact volume of a liquid that is expelled from the syringe may be also achieved in an easy and straightforward manner.
  • delivery of an exact volume of a liquid, e.g. of an injectable liquid medicament, contained in the chamber after reconstitution may be facilitated.
  • the exact volume may be expelled from the syringe by moving the plunger relative to the syringe barrel.
  • the first syringe section is connectable to the orifice of the first syringe in a fluid conducting manner by fastening, e.g. connecting or fixing, the fastening structure of the first syringe to the first counter fastening structure of the first syringe section.
  • At least one of the first syringe and the second syringe may comprise a closure fastened to the orifice, wherein the closure is at least one of breakable, pierceable and detachable. This way, a contamination of the lyophilized and/or reconstitutable pharmaceutical product contained in the chamber may be prevented.
  • the closure of the at least one of the first syringe and the second syringe may be at least one of broken, pierced and detached from the orifice, e.g.
  • the closure may comprise at least one of a seal, a septum, a screw cap and a plug.
  • the second syringe section comprising a second counter fastening structure
  • the second syringe section is connectable to the orifice of the second syringe in a fluid conducting manner by fastening, e.g. connecting or fixing, the fastening structure of the second syringe to the second counter fastening structure of the second syringe section.
  • the number of sections may comprise a discharge section connectable to a medicament container in a fluid conducting manner.
  • the injectable liquid medicament contained in the number of syringes after completion of the reconstitution process may be transferred into the medicament container without needed to disconnect the respective syringe from the merging adapter. This way, the risk of contamination or loss of injectable liquid medicament may be reduced. Further, a high sterility of the preparation process may be obtained.
  • There medicament container may comprise an intravenous (IV) infusion bag.
  • IV intravenous
  • At least one of the syringe sections, the diluent feed section and the discharge section may comprise a flexible tube, e.g., a flexible hose.
  • Flexible tubing may allow at least one of a shaking and rolling of at least one of the number of syringes without needed to disconnect the respective syringe from the merging adapter. This way, the risk of contamination or loss of injectable liquid medicament may be reduced. Further, a high sterility of the preparation process may be obtained.
  • flexible tubing may facilitate the process of connecting the multiple syringes to the merging adapter and/or connecting the diluent container to the merging adapter and/or connecting the medicament container to the merging adapter.
  • an independent shaking or rolling of a syringe may be allowed without shaking or rolling at least of another syringe, the diluent container and the medicament container.
  • a material of the flexible tube may be a deformable plastic material, which is pharmaceutically inert.
  • At least one of the syringe sections, the diluent feed section and the discharge section may be provided with at least one of a valve and a clamp, e.g. a tube clamp, to control a fluid flow through the respective section. Via the valve or clamp a fluid flow through the respective section may be prevented or allowed. By this, an undesired flow of liquid may be prevented. For example, after initially filling the number of syringes with a specific amount of liquid from the diluent container, a further liquid flow out of the diluent container into the syringes may be prevented by the closing the valve or clamp provided in the diluent feed section. Further, by the closing the valve or clamp an undesired flow of liquid from the syringes back into the diluent container may be prevented.
  • a valve and a clamp e.g. a tube clamp
  • the diluent feed section may be provided with check valve that allows a fluid flow out of the diluent container but prevents a fluid flow back into the diluent container.
  • the discharge section may be provided with check valve that allows a fluid flow into the medicament container but prevents a fluid flow out of the medicament container.
  • At least one of the syringe sections, the diluent feed section and the discharge section may comprise a self-closing port, e.g., a self-closing Luer-Lock port.
  • the self-closing Luer-Lock port may include a Luer-Lock fitting and a Luer activated valve.
  • the Luer activated valve may enable at least one of an unidirectional flow and a bidirectional flow when connected with a Luer-Lock counter fitting compatible to the Luer-Lock fitting of the self-closing Luer-Lock port.
  • At least one of the syringe sections, the diluent feed section and the discharge section may comprise a pre-attached closure, e.g., a pre-attached Luer-Lock plug.
  • the closure may have to be removed from the respective section to get access to the section. This way, the respective section is sealed per default and the closure has to be removed when the respective section should be used.
  • the number of syringes may be smaller than the number of the syringe sections of the fluid line of the merging adapter.
  • at least one of the syringe sections may be provided with a valve, a clamp, a self-closing port or a closure for preventing a fluid flow through this syringe section, e.g., when the respective section is not connected to a syringe.
  • At least one of the valve or clamp may be actuable.
  • the number of syringes and at least one of the diluent feed section and the discharge section may be configured such that the plungers need to be actuated actively in order to transfer liquid into or from the chambers.
  • movement of a plunger of one of the number of syringes may not result in a movement of another one of the number of syringes but will instead transfer liquid from or into the diluent container and/or from or into the medicament container.
  • valves or clamps provided in the syringe sections may not be needed as an undesired liquid flow is prevented as a liquid flow into or from a syringe will only take place when the plunger of the respective syringe is actuated actively.
  • the discharge section may directly or indirectly connectable to a diluent feed section of another merging adapter, e.g. another merging adapter of another reconstitution kit as described above, and/or the diluent feed section of the same merging adapter.
  • another merging adapter e.g. another merging adapter of another reconstitution kit as described above
  • the diluent feed section of the same merging adapter may be directly or indirectly connectable to a diluent feed section of another merging adapter, e.g. another merging adapter of another reconstitution kit as described above, and/or the diluent feed section of the same merging adapter.
  • This may allow concatenating multiple merging adapters and this way of multiple reconstitution kits. This way, the number of syringes that may be a filled with a reconstituting liquid in a single filling process may be increased.
  • a reconstitution kit for preparing an injectable liquid medicament may be pooled with another reconstitution kit
  • the discharge section may comprise a discharge section fastening structure and/or the diluent feed section may comprise a feed section fastening structure.
  • the diluent container may be fastened, e.g., connected or fixed, to the merging adapter.
  • the diluent container may comprise a counter fastening structure complementary shaped to the feed section fastening structure.
  • a medicament container may be fastened, e.g., connected or fixed, to the merging adapter.
  • the medicament container may comprise a counter fastening structure complementary shaped to the discharge section fastening structure.
  • the feed section fastening structure may be complementary shaped to the discharge section fastening structure. This may allow a direct interconnection of the discharge section of the merging adapter to the diluent feed section of another merging adapter another reconstitution kit as described above. Further, this may allow to connect the discharge section to the diluent feed section of the same merging adapter in a fluid conducting manner. This way an endless fluid line, e.g. in form of a closed loop, may be formed, e.g. for transporting the reconstitution kit filled with a liquid, e.g., filled with a reconstituted injectable liquid medicament.
  • the reconstitution kit may comprise an interconnector, wherein the interconnector comprises a fluid passage section, wherein a first connecting portion of the interconnector is fastenable to the discharge section fastening structure of the merging adapter and a second connecting portion of the interconnector is fastenable to the feed section fastening structure of the another merging adapter, such that the discharge section of the merging adapter is connectable to the diluent feed section of the another merging adapter in a fluid conducting manner via the fluid passage section.
  • the interconnector may allow to connect the discharge section to the diluent feed section of the same merging adapter in a fluid conducting manner. This way an endless fluid line may be formed, e.g. for transporting the reconstitution kit filled with a liquid, e.g., filled with a reconstituted injectable liquid medicament.
  • a positive-locking fit or a frictional fit may be provided between at least one of the fastening structure of the first syringe and the first counter fastening structure, the fastening structure of the second syringe and the second counter fastening structure, and the discharge section fastening structure and the feed section fastening structure.
  • the fit may be at least one of a screw type fit, a bayonet fit and a Luer-Lock fit.
  • the merging adapter may be a sterile, single-use adapter.
  • the lyophilized and/or reconstitutable pharmaceutical product may be provided as a powdered substance or cake-like substance.
  • a material of the syringe body may be a glass material, a vitreous material or a dimensionally stable plastic material, which are pharmaceutically inert.
  • the syringe body may comprise a barrel made of Cyclic Olefin Polymer (COP) or Cyclic Olefin Copolymer (COCP).
  • COP Cyclic Olefin Polymer
  • COCP Cyclic Olefin Copolymer
  • a method of preparing an injectable liquid medicament makes use of a reconstitution kit as described above.
  • the orifice of each syringe is connected to one of the number of syringe sections of the merging adapter in a fluid conducting manner by fastening the fastening structure of the respective syringe to the counter fastening structure of the respective syringe section.
  • a diluent container which is filled with a reconstituting liquid, is connected to the diluent feed section in a fluid conducting manner.
  • the reconstituting liquid is brought in contact with the lyophilized and/or reconstitutable pharmaceutical product contained in each syringe by moving the plunger of each syringe.
  • the method of preparing the injectable liquid medicament is conducted by making use of a reconstitution kit as described above.
  • all effects, features and benefits as described above in connection with the reconstitution kit equally apply to the method of preparing the injectable liquid medicament; and vice versa.
  • the dissolving/reconstitution process may be accelerated or enhanced by shaking or rolling at least one of the number of syringes.
  • the dissolving/reconstitution process may be accelerated or enhanced by generating a liquid exchange flow between the chambers of at least two syringes by moving the plungers of the at least two syringes.
  • the liquid may be draw out, e.g. sucked out, from the diluent container via the diluent feed section by moving the plunger of at least one of the syringes.
  • At least a portion of the injectable liquid medicament from the chamber of at least one of the number of syringes may be transferred into the diluent container via the diluent feed section by moving the plunger of the at least one syringe.
  • liquid injectable medicament from the chamber of each syringe may be transferred into the diluent container via the diluent feed section by moving the plunger of each syringe.
  • the diluent container may be disconnected from the diluent feed section and a medicament container may be connected to the diluent feed section. Afterwards, at least a portion of the injectable liquid medicament from the chamber of at least one of the number of syringes may be transferred into the medicament container via the diluent feed section by moving the plunger of the at least one syringe. In a further example, the liquid injectable medicament from the chamber of each syringe may be transferred into the medicament container via the diluent feed section by moving the plunger of each syringe.
  • the number of sections may comprise a discharge section connectable to a medicament container in a fluid conducting manner.
  • a medicament container may be connected to the discharge section in a fluid conducting manner and at least a portion of the injectable liquid medicament from the chamber of at least one of the number of syringes may be transferred into the medicament container via the discharge section by moving the plunger of the at least one syringe.
  • the medicament container may be disconnected from the discharge section.
  • Another medicament container may be connected to the discharge section.
  • At least a portion, e.g., the remaining portion, of the injectable liquid medicament from the chamber of at least one of the number of syringes may be transferred into the another medicament container via the discharge section by moving the plunger of the at least one syringe.
  • liquid injectable medicament from the chamber of each syringe may be transferred into the medicament container via the discharge section by moving the plunger of each syringe.
  • At least one of the diluent container and the medicament container may be a flexible bag.
  • a flexible bag allows for a rather easy and durable storage as well as transportation of a liquid, e.g., a liquid diluent or an injectable liquid medicament, contained therein.
  • the reconstitution process may be simplified or facilitated, e.g. by squeezing portions of the flexible bag.
  • the reconstitution process may be simplified or facilitated as a container volume of a flexible bag may change.
  • connecting the diluent container to the merging adapter may be carried out before connecting the syringes to the merging adapter.
  • a system for preparing an injectable liquid medicament comprises a reconstitution kit as described above.
  • a reconstitution kit as described above.
  • the system comprises a reconstitution apparatus.
  • the reconstitution apparatus comprises a merging adapter seat for the merging adapter of the reconstitution kit.
  • the merging adapter seat comprises a feed section seat configured to receive the diluent feed section of the merging adapter.
  • the merging adapter seat further comprises a number of syringe section seats, wherein the number of syringe section seats comprises syringe section seats configured to receive the number of syringe sections of the merging adapter.
  • the apparatus further comprises a number of syringe seats, wherein each syringe seat is assigned to one of the number of syringe section seats, wherein the number of syringe seats comprises syringe seats configured to receive the number of syringes of the reconstitution kit when the syringe is connected to the respective syringe section.
  • Each syringe seat is provided with a plunger actuator that is configured to move the plunger of the syringe received in the syringe seat to transfer liquid into and from the chamber of the respective syringe through the orifice upon movement of the plunger.
  • the number of syringe section seats may be greater than the number of the syringe sections of the fluid line of the merging adapter.
  • Making use of the system preparing of an injectable liquid medicament may be facilitated and/or accelerated.
  • the preparation of an injectable liquid medicament using the reconstitution kit as described above may be automated, e.g., transferring liquid into and out of the chamber of the respective syringe may be performed by actuating the respective plunger actuator.
  • the apparatus could be a simple tabletop device.
  • the actuators may be electrically driven to operate the syringe received or installed in the respective syringe seat by a driving the plunger syringe.
  • the merging adapter seat may comprise a discharge section seat configured to receive the discharge section of the merging adapter.
  • At least one of the number of syringe section seats, the feed section seat and the discharge section seat may be provided with an actuatable section clamp, the respective actuatable section clamp being transferable between a closed state preventing a fluid flow through the respective section to an open state allowing a fluid flow through the respective section.
  • actuating a section clamp the respective section may be closed off.
  • the fluid connection between the component connected to the respective section e.g., one of the syringes, the diluent container, the medicament container, may be isolated from the remaining components connected to the merging adapter in order to prevent a fluid flow from or into the component (closed off component).
  • a backflow of liquid, e.g., injectable liquid medicament, into the diluent container may be prevented by transferring the section clamp provided in the feed section seat from the open state into the closed state.
  • one of the number of syringes may be closed off from the merging adapter by transferring the section clamp provided in the respective syringe section seat from the open state into the closed state prior to or during an initial filling process of the reconstitution kit with a diluent from a diluent container, e.g. to provide a spare volume within the merging adapter. This spare volume may be used for subsequent mixing process.
  • a liquid exchange flow may be generated between the chambers of at least two syringes by actuating at least two actuators .
  • the apparatus may comprise at least on one sensor configured to monitor the status of reconstitution of the lyophilized and/or reconstitutable pharmaceutical product of at least one of the syringes.
  • the at least one sensor may be an optical sensor, e.g., an opacity sensor.
  • At least one of the syringe seats may be provided with an installation sensor configured to detect whether a syringe is received, e.g., installed, in the syringe seat.
  • At least one syringe may be provided with an identification label, wherein the identification label comprises information concerning the lyophilized and/or reconstitutable pharmaceutical product contained in the syringe and/or in the reconstitution kit, e.g. drug type or dose.
  • the identification label may be at least one of an electronic label, e.g. in form of an RFID-chip or RFID-label, or an optical label, e.g., a barcode or a quick response (QR) code.
  • At least one of the syringe seats may be provided with an identification label reader configured to read out the information included in the identification label.
  • the apparatus may further comprise a controller, wherein the controller is configured to at least one of controlling the operation the number of actuators in order to transfer liquid into and from the chamber of the respective syringe through the orifice upon movement of the plunger by the respective actuator, and controlling the operation of the one or more actuatable section clamps. Via the controller the reconstitution process and this way the preparation process of the injectable liquid medicament may be automated.
  • the controller may be provided with at least one predefined reconstitution program that may include commands to open and close respective section clamps and/or actuating the plunger actuators in a predefined sequence in order to end up with the injectable liquid medicament.
  • the controller may be provided with a multiple predefined reconstitution programs each adapted to one or more specific reconstitution kits.
  • At least one of the syringe section seats, the feed section seat and the discharge section seat may comprise a recess, e.g., a receiving bay for accommodation of the syringe section, the feed section and the discharge section respectively.
  • At least one of the syringe seats may comprise a recess, e.g., a receiving bay for accommodation of the respective syringe.
  • each syringe is connected to one of the number of syringe sections of the merging adapter in a fluid conducting manner by fastening the fastening structure of the respective syringe to the counter fastening structure of the respective syringe section.
  • a diluent container which is filled with a reconstituting liquid, is connected to the diluent feed section in a fluid conducting manner.
  • the merging adapter is arranged in the reconstitution apparatus such that the diluent feed section is received in the feed section seat and such thar the number of syringe sections is received in the number of syringe section seats.
  • the number of syringes is arranged such that the number of syringes is received in the number of syringe section seats.
  • the actuators are actuated in order to transfer liquid into the chamber of the respective syringe through the orifice upon movement of the plunger, such that the reconstituting liquid is brought in contact with the lyophilized and/or reconstitutable pharmaceutical product contained in each syringe.
  • the actuators When actuating the actuators, the actuators may be actuated such that an alternating exchange liquid flow is provided between at least two syringes, e.g., by controlling the section clamps and the actuators of each syringe accordingly.
  • Such kind of alternating exchange liquid flow may be generated between different combinations of syringes, e.g., by controlling the section clamps and the actuators accordingly. This way, dissolving and mixing may be enhanced and/or accelerated.
  • At least one of the first syringe and the second syringe may comprise a closure fastened to the orifice, wherein the closure is at least one of breakable, pierceable and detachable.
  • the method may comprise the step of at least one of breaking, piercing and detaching of the closure from the orifice of the at least one of the first syringe and the second syringe.
  • the step of at least one of breaking, piercing and detaching of the closure from the orifice of the at least one of the first syringe and the second syringe may be conducted prior to or upon connecting the at least one of the first syringe and the second syringe to the syringe section of the merging adapter.
  • the method may include the step of actuating at least one actuator such that liquid is transferred into and from the chamber of at least one syringe at least two times. This way, dissolving and mixing may be enhanced and/or accelerated.
  • At least a portion of the injectable lyophilized medicament may be transferred back into the diluent container or into a medicament container.
  • the method may include initially transferring the reconstituting liquid from the diluent container into the chambers of the number of syringes such that a spare volume remains in at least one of the number of syringes by not or only partially filling the at least one syringe with the liquid.
  • the fluid connection between the diluent container and the diluent feed section may be closed off.
  • a liquid exchange flow between the chambers of at least two syringes may be generated by actuating at least two actuators. This way dissolving and mixing may be enhanced and/or accelerated.
  • the fluid connection between the diluent container and the diluent feed section may be restored in order to fill the spare volume with reconstituting liquid.
  • the method steps do not necessarily have to be executed in the aforementioned order.
  • the merging adapter may be arranged in the reconstitution apparatus before connecting the syringes to the merging adapter.
  • 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.
  • 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.
  • 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.
  • 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.
  • the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • an insulin e.g., human insulin, or a human insulin analogue or derivative
  • GLP-1 glucagon-like peptide
  • DPP4 dipeptidyl peptidase-4
  • 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".
  • 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.
  • 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.
  • insulin analogues examples include 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.
  • 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-g
  • GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697
  • 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.
  • DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
  • 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.
  • Gonadotropine Follitropin, Lutropin, Choriongonadotropin, Menotropin
  • Somatropine Somatropin
  • Desmopressin Terlipressin
  • Gonadorelin Triptorelin
  • Leuprorelin Buserelin
  • Nafarelin Nafarelin
  • Goserelin Goserelin.
  • 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.
  • 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.
  • antibody refers to an immunoglobulin molecule or an antigenbinding portion thereof.
  • 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.
  • the antibody has effector function and can fix complement.
  • the antibody has reduced or no ability to bind an Fc receptor.
  • 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).
  • TBTI tetravalent bispecific tandem immunoglobulins
  • CODV cross-over binding region orientation
  • fragment refers 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.
  • SMIP small modular immunopharmaceuticals
  • 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.
  • 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).
  • VH domain or VHH domain single heavy chain variable domain
  • VL domain single light chain variable domain
  • An immunoglobulin single variable domain 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.
  • 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.
  • Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.
  • 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).
  • 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”).
  • VHH 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).
  • CDR complementarity-determining region
  • 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.
  • 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.
  • antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
  • PCSK-9 mAb e.g., Alirocumab
  • anti IL-6 mAb e.g., Sarilumab
  • anti IL-4 mAb e.g., Dupilumab
  • 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.
  • 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.
  • 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).
  • a single-dose container system may involve a needle-based injection device with a replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • Fig. 1 schematically a reconstitution kit comprising four syringes and a merging adapter
  • Fig. 2 schematically illustrates the reconstitution kit shown in Fig. 1, a diluent container and a discharge container in a preparation arrangement for performing a process of preparing an injectable liquid medicament in a first state
  • FIG. 3 schematically illustrates the preparation arrangement of Fig. 2 in a second state chronologically after the first state
  • Fig. 4 schematically illustrates the preparation arrangement of Fig. 2 in a third state chronologically after the second state
  • Fig. 5 schematically illustrates an arrangement of two reconstitution kits and an interconnector in a separate arrangement
  • Fig. 6 schematically illustrates the arrangement of Fig 5 in an interconnected arrangement
  • Fig. 7 schematically illustrates another example of a merging adapter of another reconstitution kit
  • Fig. 8 schematically illustrates a reconstitution system comprising a reconstitution apparatus and another example of a reconstitution kit
  • FIG. 9 schematically illustrates the reconstitution apparatus as shown in Fig. 8,
  • Fig. 10 schematically illustrates the reconstitution system as shown in Fig. 8, a diluent container and a discharge container in a preparation arrangement for performing a process of preparing an injectable liquid medicament in an initial state
  • Figs. 11a-11h schematically illustrate the preparation arrangement of Fig. 10 in consecutive states when performing the process of preparing an injectable liquid medicament
  • Fig. 12 schematically illustrates a syringe for a reconstitution kit.
  • the reconstitution kit 100 as shown in Figs. 1-4 comprises a number of substantially identical syringes 10, namely a first syringe 10a, a second syringe 10b, a third syringe 10c and a fourth syringe 10d.
  • the number of syringes 10 comprises four syringes 10.
  • Each syringe 10 comprises a syringe body 11 in form of a barrel defining a chamber 12 containing lyophilized and/or reconstitutable pharmaceutical product 1 in form of a cake.
  • This lyophilized and/or reconstitutable pharmaceutical product 1 may be reconstituted by bringing the pharmaceutical product 1 in contact with a reconstituting liquid 3, e.g., water for infusion or saline.
  • Each syringe 10 comprises a discharge end 13, wherein the discharge end 13 comprises a fastening structure 14.
  • Each syringe 10 further comprises a plunger 16, e.g., a piston, which is slidably received within the syringe body 11. Upon movement of the plunger 16 liquid may be transferred into and out from the chamber 12 through the orifice 15.
  • the reconstitution kit 100 further comprises a merging adapter 30 adapted to be connected to the syringes 10 of the reconstitution kit 100 in order to provide a fluid connection between the chambers 12 of the number of syringes 10.
  • the merging adapter 30 comprises a fluid line 40, wherein the fluid line 40 comprises a number of sections 41, 44, 47.
  • the number of sections 41, 44, 47 are interconnected in a fluid conducting a manner.
  • the number of sections 41, 44, 47 comprise a number of syringe sections 41 for connecting the number of syringes 10, namely a first syringe section 41a for the first syringe 10a, a second syringe section 41b for the second syringe 10b, a third syringe section 41c for the third syringelOd, and a fourth syringe section 41 d for the fourth syringe 10d.
  • the number of syringe sections 41 comprises four syringe sections 41.
  • Each syringe section 41 is connectable to one syringe 10 of the number of syringes 10.
  • the first syringe section 41a is connectable to the orifice 15 of the first syringe 10a in a fluid conducting manner, wherein the first syringe section 41a comprises a first counter fastening structure 42a which is complementary shaped to the fastening structure 14 of the first syringe 10a.
  • the second syringe section 41b is connectable to the orifice 15 of the second syringe 10b in a fluid conducting manner, wherein the second syringe section 41b comprises a second counter fastening structure 42b, wherein the second syringe section 41b complementary shaped to the fastening structure 14 of the second syringe 10b.
  • the fastening structures 14 of the syringes 10 may be shaped substantially identical and the counter fastening structures 42 of the syringe sections 41 may be shaped substantially identical, such that each syringe 10 can be connected to each syringe section 41 in a fluid conducting manner.
  • each syringe 10 comprise a male Luer-Lock fitting and each the counter fastening structures 42 of each syringe section 41 comprises a female Luer-Lock fitting.
  • the number of sections 41 , 44, 47 further comprises a diluent feed section 44, wherein the diluent feed section 44 is connectable to a diluent container 50, e.g., a flexible bag, in a fluid conducting manner, as shown in Fig. 2.
  • a diluent container 50 e.g., a flexible bag
  • the diluent feed section 44 comprises a feed section fastening structure 45 and the diluent container 50 comprises a counter fastening structure 55 complementary shaped to the feed section fastening structure 45.
  • the counter fastening structure 55 may comprise a male Luer-Lock fitting and feed section fastening structure 45 may comprise a female Luer-Lock fitting.
  • the number of sections 41 , 44, 47 further comprises a discharge section 47, wherein the discharge section 44 is connectable to medicament container 60, e.g., a flexible infusion bag, in a fluid conducting manner, as shown in the Fig. 2.
  • medicament container 60 e.g., a flexible infusion bag
  • discharge section 47 comprises a discharge section fastening structure 48 and the medicament container 60 comprises a counter fastening structure 65 complementary shaped to the discharge section fastening structure 48.
  • the counter fastening structure 65 may comprise male Luer-Lock fitting and feed section fastening structure 48 may comprise a female Luer-Lock fitting.
  • Each syringe section 41, the feed section 44 and the discharge section 47 comprise a flexible tube.
  • the reconstitution kit 100 may be used for preparation of an injectable liquid medicament 2.
  • the number of syringes 10 containing lyophilized/reconstitutable pharmaceutical product 1 may be simultaneously filled with a liquid, e.g., a reconstituting liquid 3, by connecting the number of syringes 10 and a diluent container 50, which is filled with the reconstituting liquid 3, to the merging adapter 30 as shown in Fig. 2.
  • a liquid e.g., a reconstituting liquid 3
  • the chambers 12 of the number of syringes 10 are in fluid connection to one another via the fluid line 40 of the merging adapter 30 and in fluid connection with the diluent feed section 44.
  • This concept allows a fluid flow from the diluent container 50 that is a connected to the diluent feed section 44 into the chambers 12 of the number of syringes 10, e.g. via drawing the reconstituting liquid 3 from the diluent container 50 into the chambers 12 of the syringes 10 by moving the plungers 16 as illustrated in Fig. 3.
  • the lyophilized/reconstitutable pharmaceutical product 1 will start to reconstitute upon contact with the reconstituting liquid 3.
  • an injectable liquid medicament 2 is obtained in the chambers 12 of the syringes 10.
  • the dissolving/reconstitution process may be accelerated or enhanced by gently shaking or gently rolling the syringes 10.
  • the diluent feed section 44 comprises a valve 46 and the discharge section 47 comprises another valve 46.
  • the syringe sections 42 are free of valves.
  • the respective valve 46 is on/off valve that is transferrable from a closed state preventing a fluid flow through the respective section 44, 47 to an open state allowing a fluid flow through the respective section 44, 47. Via the valves 46 the diluent container 50 and the medicament container 60 may be closed off from the fluid line 40 such that a liquid flow from or into the diluent container 50 and from or into the medicament container 60 is prevented.
  • valve 46 of the diluent feed section 44 When initially filling the syringes 10, the valve 46 of the diluent feed section 44 is in the open state and the valve 46 of the discharge section 47 may be in the closed state. This way, the reconstituting liquid 3 may be drawn from the diluent container 50 into the chambers 12 of the syringes 10 by moving the plungers 16 as illustrated in Fig. 4., wherein a liquid flow from the medicament container 60 into the chambers 12 of the syringes 10 is prevented.
  • valve 46 of the diluent feed section 44 may be transferred in the closed state to prevent a back flow into the diluent container 50, especially when the plungers 16 are moved in order to provide an exchange flow between the syringes 10.
  • the valve 46 of the diluent feed section 44 may be transferred or remain in the closed state and the valve 46 of the discharge section 47 is transferred into the open state.
  • the injectable liquid medicament 2 contained in the syringes 10 may then be transferred into the medicament container 60 via the discharge section 47 by moving the plungers 16 such that the injectable liquid medicament 2 is expelled from each syringe 10 as illustrated in Fig. 4.
  • the discharge section 47 may directly or indirectly connectable to a feed section 45 of another merging adapter 30’ of another reconstitution kit 100’ as shown in Figs. 5 and 6.
  • a reconstitution kit 100 for preparing an injectable liquid medicament 2 may be pooled with another reconstitution kit 100’ for preparing another injectable liquid medicament 2.
  • different reconstitution kits 100, 100’ may be pooled and reconstituted in an easy and sterile manner. In the example shown in Figs.
  • the reconstitution kit 100 comprises an interconnector 70, wherein the interconnector 70 comprises a fluid passage section 73, a first connecting portion 71 for the merging adapter 30 and a second connecting portion 72 for the another merging adapter 30’.
  • the discharge section 47 of the merging adapter 30 is connectable to the first connecting portion 71 of the interconnector and the feed section 44 of the another merging adapter 30’ is connectable to the second connecting portion 72 of the interconnector 70, such that the discharge section 47 of the merging adapter 30 is connected to the diluent feed section 44 of the another merging adapter 30’ in a fluid conducting manner via the fluid passage section 73.
  • the first connecting portion 71 comprises a female Luer-Lock fitting fastenable to the discharge section fastening structure 48 of the merging adapter 30 comprising a male Luer-Lock fitting and the second connecting portion 72 comprises a female Luer-Lock fitting fastenable to the feed section fastening structure 45 of the another merging adapter 30’ comprising a male Luer-Lock fitting.
  • Fig. 7 shows another example of a reconstitution kit 100, a diluent container 50 and a medicament container 60.
  • the example of the reconstitution kit 100 as shown in Fig. 7 is substantially identical to the reconstitution kit 100 shown in Figs. 1-4, but comprises only three syringes 10.
  • one of the four syringe sections 41 remains free of a syringe 10.
  • Each syringe section 41 is provided with a valve 46.
  • the valves 46 provided in the syringe sections 41 are on/off valves transferrable from a closed state preventing a fluid flow through the respective syringe section 41 to an open state allowing a fluid flow through the respective syringe section 41 individually.
  • valves instead of valves, removable closures, such as Luer-Lock plugs, may be used, e.g., Luer-Lock plugs that are pre-attached to the syringe sections and which are only to be removed if the syringe section is used.
  • Luer-Lock plugs that are pre-attached to the syringe sections and which are only to be removed if the syringe section is used.
  • Fig. 8 shows a system 300 for preparing an injectable liquid medicament 2 making use of another example of a reconstitution kit 100.
  • the example of the reconstitution kit 100 as shown in Fig. 8 is substantially identical to the example of the reconstitution kit 100 as shown in Figs. 1-4, but is free of any valves 46.
  • the system 300 further comprises a reconstitution apparatus 200 that is adapted to the reconstitution kit 100.
  • the apparatus 200 is shown in more detail in Fig. 9.
  • the apparatus 200 comprises a merging adapter seat 240 for the merging adapter 30 of the reconstitution kit 100 configured to receive, e.g., accommodate, the merging adapter 30.
  • the adapter seat 240 comprises a feed section seat 244 configured to receive the feed section 44 of the merging adapter 30, four syringe section seats 241 , wherein each syringe section seat 241 is configured to receive one of the four syringe sections 41 of the merging adapter 30, and a discharge section seat 247 configured to receive the discharge section 47 of the merging adapter 40.
  • the syringe section seats 241 , the feed section seat 244, the discharge section seat 247 and the syringe seat 210 may be shaped in form of a recess.
  • the apparatus 200 further comprises four syringe seats 210, wherein each syringe seat 210 is assigned to one of the number of syringe section seats 241, wherein each syringe seat 210 is configured to receive one of the syringes 10 of the reconstitution kit 100 when the syringes 10 are connected to the syringe sections 41.
  • Each syringe seat 210 is provided with a plunger actuator 216 that is configured to move the plunger 16 of the syringe 10 received in the syringe seat 210 to transfer liquid into and from the chamber 12 of the respective syringe 10 through the orifice 15 upon movement of the plunger 16.
  • the syringe section seats 241 , the feed section seat 244 and the discharge section seat 247 are provided with an actuatable section clamp 246, e.g. a tube clamp, each.
  • the respective actuatable section clamp 246 may be transferable between a closed state preventing a fluid flow through the respective section 41, 44, 47 to an open state allowing a fluid flow through the respective section 41, 44, 47.
  • the clamp 246 may be configured to squeeze the respective section 41 , 44, 47 in the closed state in order to prevent the fluid flow.
  • the apparatus 200 further comprises a controller 206, e.g. an electronic controller, wherein the controller 206 is configured to control the operation the number of actuators 216 in order to transfer liquid into and from the chamber 12 of the respective syringe 10 through the orifice 15 upon movement of the plunger 16 by the respective actuator 216, and to control the operation of the one or more actuatable section clamps 246.
  • the actuators 216 may comprise an electric motor 204, wherein the controller 206 controls the motors 204 in order to actuate the actuators 216.
  • a preparation of an injectable liquid medicament 2 may be facilitated and/or accelerated.
  • the preparation of an injectable liquid medicament using the reconstitution kit 100 as described above may be automated, e.g., transferring liquid into and out of the chamber 12 of the respective syringe 10 may be performed by actuating the respective plunger actuator 216.
  • the controller 206 Via the controller 206 the reconstitution process and this way the preparation of the injectable liquid medicament 1 may be automated.
  • the controller 206 may be provided with at least one predefined reconstitution program that may include commands to open and close respective clamps 246 and/or actuating the plunger actuators 216 in a predefined sequence in order to end up with a final injectable liquid medicament 2.
  • the controller 206 may be provided with several predefined reconstitution programs each adapted to one or more specific reconstitution kits 100.
  • the reconstitution kit 100 may be inserted into the apparatus 200 as shown in Fig. 10. Further, a diluent container 50, which is filled with a reconstituting liquid 3, and a medicament container 60 are connected to merging adapter 30 in a fluid conducting manner. In an initial state, shown in Fig. 10, all of the clamps 246 are in the open state. This may facilitate insertion of the reconstitution kit 100 into the apparatus 200.
  • a portion of the reconstituting liquid 3 is drawn into the chambers 12 of the syringes 10 with exception of the most right syringe 10 by actuating the plunger actuators 216 assigned to the three most left syringes 10 (Fig. 11b).
  • This spare volume is provided by the most right syringe 10. This spare volume may be used for a subsequent mixing process as described in more detail below.
  • the diluent feed section 44 is closed off by transferring the respective clamp 246 into the closed state and the most right syringe section 41 is opened up by transferring the respective clamp 246 into the open state (Fig. 11c).
  • a liquid flow is provided from the most left syringe 10 to the most right syringe 10 by actuating the plunger actuators 216 assigned to the most left syringe 10 and to the most right syringe 10 (Figs. 11 d and 11 e).
  • an exchange flow is provided between at least two syringes 10 by actuating the plunger actuators 216 assigned to the respective syringes 10 (Fig. 11 f).
  • a mixing process may be generated.
  • An alternating flow of liquid may be provided in each syringe 10 to enhance and accelerate the reconstitution process.
  • each syringe contains an injectable liquid medicament 2 and the clamp 246 assigned to the discharge section seat 247 may be transferred into the open state (Fig. 11g).
  • the injectable liquid medicament 2 contained in each syringe 10 is transferred into the medicament container 60 by expelling the injectable liquid medicament 2 by actuating the plunger actuators 216 (Fig. 11h).
  • the medicament container 60 may be disconnected from the merging adapter 30, e.g. to transport the medicament container 60, which is filled with the injectable liquid medicament 2, to the patient for administration.
  • additional reconstitution liquid 3 may be drawn into the merging adapter 30 and thus into the chambers 12 during the preparation process by transferring the clamp 246 of the syringe section seat 244 into the open state and actuating at least one plunger actuator 216.
  • Fig. 12 shows a syringe 10 that may form a syringe 10 of one of the reconstitution kits 100 as outlined above.
  • the syringe 10 comprises a syringe body 11 in form of a barrel defining a chamber 12 containing lyophilized and/or reconstitutable pharmaceutical product 1 in form of a cake.
  • This lyophilized and/or reconstitutable pharmaceutical product 1 may be reconstituted by bringing the pharmaceutical product 1 in contact with a reconstituting liquid 3, e.g., water for infusion or saline.
  • the syringe 10 comprises a discharge end 13, wherein the discharge end 13 comprises a fastening structure 14.
  • the syringe 10 further comprises a plunger 16, e.g., a piston, which is slidably received within the syringe body 11. Upon movement of the plunger 16 a liquid may be transferred into and out from the chamber 12 through an orifice 15 of the discharge end 13.
  • a plunger 16 e.g., a piston
  • the syringe 10 comprises a closure 17 fastened to the orifice 15, wherein the closure 17 is at least one of breakable, pierceable and detachable.
  • the closure 17 may comprise at least one of a seal, a septum, a screw cap and a plug.
  • the closure 17 of the a syringe 10 may be at least one of broken, pierced and detached from the orifice 15, e.g. prior to or upon connecting the syringe 10 to one of the syringe sections 41 of the merging adapter 40, to allow the transfer of the liquid 3 into and from the chamber 12 of the syringe 10 through the orifice 15 of the syringe 10.

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  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un kit de reconstitution (100) pour la préparation d'un médicament liquide injectable (2), le kit de reconstitution (100) comportant : plusieurs seringues (10) y compris au moins une première seringue (10a) et une seconde seringue (10b), chaque seringue (10) comprenant un corps de seringue (11) définissant une chambre (12) contenant un produit pharmaceutique lyophilisé et/ou reconstituable (1) ; une extrémité d'évacuation (13), l'extrémité d'évacuation (13) comprenant une structure de fixation (14) et un orifice (15) ; un piston (16) reçu de manière coulissante à l'intérieur du corps de seringue (11) servant à transférer un liquide dans et depuis la chambre (12) à travers l'orifice (15) lors du mouvement du piston (16) ; et un adaptateur de fusion (30), l'adaptateur de fusion (30) comprenant une conduite de fluide (40), la conduite de fluide (40) comprenant un certain nombre de sections (41, 44, 47), le nombre de sections (41, 44, 47) étant interconnecté de manière conductrice de fluide. Le nombre de sections (41, 44, 47) comprend plusieurs sections de seringue (41) permettant de relier le nombre de seringues (10), les plusieurs sections de seringue (41) comportant au moins : une première section de seringue (41a), la première section de seringue (41a) pouvant être reliée à l'orifice (15) de la première seringue (10a) d'une manière conductrice de fluide, la première section de seringue (41a) comprenant une première structure de contre-fixation (42a) de forme complémentaire à la structure de fixation (14) de la première seringue (10a) ; une seconde section de seringue (41b), la seconde section de seringue (41b) pouvant être reliée à l'orifice (15) de la seconde seringue (10b) d'une manière conductrice de fluide, la seconde section de seringue (41b) comprenant une seconde structure de contre-fixation (42b), la seconde section de seringue (41b) étant de forme complémentaire à la structure de fixation (14) de la seconde seringue (10b) ; une section d'alimentation en diluant (44), la section d'alimentation en diluant (44) pouvant être reliée à un récipient de diluant d'une manière conductrice de fluide.
PCT/US2025/025336 2024-04-19 2025-04-18 Kit de reconstitution pour la préparation d'un médicament liquide injectable, système de préparation d'un médicament liquide injectable, méthodes de préparation d'un médicament liquide injectable Pending WO2025222101A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP24171200 2024-04-19
EP24171200.9 2024-04-19

Publications (1)

Publication Number Publication Date
WO2025222101A1 true WO2025222101A1 (fr) 2025-10-23

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/025336 Pending WO2025222101A1 (fr) 2024-04-19 2025-04-18 Kit de reconstitution pour la préparation d'un médicament liquide injectable, système de préparation d'un médicament liquide injectable, méthodes de préparation d'un médicament liquide injectable

Country Status (1)

Country Link
WO (1) WO2025222101A1 (fr)

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WO2006030220A1 (fr) 2004-09-17 2006-03-23 Domantis Limited Compositions monovalentes pour la liaison au cd40l et procedes d'utilisation
EP3406236A1 (fr) * 2017-05-23 2018-11-28 Metallform Werkzeugbau GmbH & Co. KG Dispositif de dosage de poches de perfusion à usage médical ainsi que dispositif de remplissage d'une pluralité de récipients vides
CN114762728A (zh) * 2021-01-12 2022-07-19 无锡诺宇医药科技有限公司 卡套、卡套动作控制装置及放射性同位素纯化/标记系统
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EP3406236A1 (fr) * 2017-05-23 2018-11-28 Metallform Werkzeugbau GmbH & Co. KG Dispositif de dosage de poches de perfusion à usage médical ainsi que dispositif de remplissage d'une pluralité de récipients vides
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