Filling unit for filling a medium, in particular in an aseptic manner

Abstract

The invention relates to a filling unit for filling a medium (2), in particular a medicament, in particular in an aseptic manner, comprising at least one container unit (3), the container interior (4) of which is closed or can be closed in a sterile manner, a sleeve (5) which closes off at least the container interior (4) from the filling unit exterior in a sterile manner, a connection (7) for introducing the medium (2) to be filled from the filling unit exterior into the sleeve (5) in a sterile manner, and a pouring unit (8) which is connected or can be connected to the connection (7) in order to pour the medium (2) which is introduced into the sleeve (5) via the connection (7) into the container interior (4).

Description

[0001] Filling unit for, in particular aseptic, filling of a medium

[0002] The present invention relates to a filling unit for, in particular aseptically, filling a medium according to claim 1, a filling device according to claim 12 for, in particular aseptically, filling a medium into a filling unit, a use according to claim 13, a use according to claim 14, a method according to claim 17 and a method for producing a filling unit according to claim 19.

[0003] In pharmaceutical production in general, and in the filling of medications and / or active ingredients in particular, there is a trend toward smaller batches and flexible systems. Filling system suppliers are therefore focusing on developing smaller and more flexible systems.

[0004] A key requirement when filling medications and / or active ingredients is to ensure freedom from germs. To this end, filling usually takes place in a protected room provided by the filling plant. In this room, the medication and / or active ingredient, the containers to be filled and the container closures are introduced into the filling plant and into the protected room via the airlocks provided for them. Any contamination must be avoided. Once introduced into the filling plant, the containers are sorted and automatically transported to the actual filling station, filled with the medication and / or active ingredient and then conveyed to a closing station where they are sealed. If the medication or active ingredient is changed, the filling station is usually extensively cleaned before filling continues with the next medication or active ingredient.

[0005] Furthermore, it is also known to provide these protected spaces through a building section which is entered and exited through locks.

[0006] Such systems and / or building sections require significant investment, require a relatively large amount of space, and are relatively complex to convert and clean, especially with smaller batches and / or frequent drug or active ingredient changes. Therefore, it is a challenge to improve the current state of the art to enable simple, safe, and cost-effective filling of media such as drugs and / or active ingredients, even with smaller batches and / or frequent drug changes.

[0007] The invention is based on the problem of simplifying the known filling of media, in particular of medicines and active ingredients, in the case of smaller batches and / or frequent changes of medicine, and of making it safe and cost-effective.

[0008] The above problem is solved by the features of claim 1.

[0009] The key idea is to provide a filling unit that includes a container unit for filling with the medium, particularly a medication and / or active ingredient, and a casing for filling. Here, the casing of the filling unit forms a protective cover for the filling process. A sterile or low-sterility space for filling is provided by the filling unit, so that the filling system itself does not need to provide a protective space for filling. The medium is filled into the casing via the connection and into the container via the filling unit within the casing. By providing a casing for the filling process, the filling system can be designed to be significantly simpler and smaller.Furthermore, this design allows the filling unit to be designed as a single-use unit, eliminating the need for time-consuming cleaning when changing media, as a different filling unit can simply be used.

[0010] The proposed filling unit serves for the, in particular aseptic, filling of a medium, in particular a medicament and / or active ingredient. It has at least one container unit, the container interior of which is or can be closed in a sterile manner. Furthermore, a sleeve is provided which sterilisingly seals at least the container interior towards the outside of the filling unit. The sleeve forms a protective cover. After the container unit has been filled and closed, it can be removed from the sleeve without contaminating the medium contained in the sealed container unit. A connection is provided for the sterile introduction of the medium to be filled from the outside of the filling unit into the sleeve. Furthermore, the filling unit has a filling unit which is connected or connectable to the connection and for filling the medium introduced into the sleeve via the connection into the container interior. The container unit is filled with this filling unit.The medium can be, in particular, liquid and / or solid substances, preferably a granulate and / or a powder and / or a liquid. In particular, the medium can be an aqueous solution and / or a soluble powder and / or an oily solution.

[0011] According to the preferred embodiment according to claim 2, the container unit comprises a container and a container closure. The container is preferably opened before filling and is closed by the container closure after filling. The provision of the container and the container closure in the sleeve enables a secure and sterile closure of the container after filling and before opening the sleeve and / or removing the container unit from the sleeve.

[0012] In the further development according to claim 3, preferred properties of the casing are described which support simple production of the filling unit and safe filling.

[0013] The provision of a holding device according to the preferred embodiment of claim 4 enables a defined alignment of the at least one container and the at least one container closure. This supports automated filling and automated closing of the container.

[0014] The provision of a container closure unit as described in claim 5 supports the automated closure of the container.

[0015] Furthermore, the automated filling and / or closing of the container is supported by a manipulator interface according to the embodiment of claim 6 and / or 7.

[0016] Preferred embodiments of the casing in the region of the manipulator interface are described in the further development according to claim 8. They enable, in particular, a relative movement of at least the manipulator interface or, in particular, the filling unit and / or the container closure unit to the at least one container.

[0017] The further development according to claim 9 enables particularly simple quality control of the filling process.

[0018] According to the further development according to claim 10, the connection can be an aseptic connection and / or the filling unit can have a pipe and / or a hose for connecting the filling unit to a reservoir. Aseptic connectors, also known as "aseptic connectors," are already known in the laboratory sector and enable a germ-free or low-germ connection, for example, of hoses.

[0019] The provision of a gas port according to claim 11 enables particularly simple testing of the casing before and / or after filling.

[0020] According to a further teaching according to claim 12, which has independent significance, a filling device is proposed for filling, in particular aseptically, a medium into a filling unit, comprising a reservoir and / or a storage holder for the medium to be filled outside the filling unit and a conveying device for conveying the medium to be filled into the filling unit. The same advantages as previously described in connection with the filling unit are achieved.

[0021] The filling unit may preferably have the features previously described in connection with the proposed filling unit, individually or in combination. Reference may be made accordingly to all statements regarding the proposed filling unit.

[0022] According to a further teaching according to claim 13, which also has independent significance, a use of a filling unit according to one of claims 1 to 11 for the aseptic filling of a medium, in particular a medicament, into at least one container unit is claimed.

[0023] Here, too, reference may be made to all the details and advantages of the proposed filling unit and the proposed filling device. According to a further teaching according to claim 14, which also has independent significance, the use of a sleeve made at least partially of plastic and / or at least partially flexible as a protective cover is proposed, in particular for providing a sterile space during the aseptic filling of a medium, in particular a medicament, into a container and / or during the closing of the container after filling the container.

[0024] The casing and / or the filling unit that provides the casing can preferably have the features previously described in connection with the filling unit, individually or in combination. Furthermore, the previously described filling unit can preferably be used for filling.

[0025] Reference may be made to all statements relating to the proposed filling unit, the proposed filling device and the proposed use.

[0026] Subclaims 15 and 16 describe preferred uses which make filling in small batches particularly cost-effective and simple.

[0027] According to a further teaching according to claim 17, which also has independent significance, a method for filling a medium, in particular aseptically, is claimed. The filling unit can have the features previously described in connection with the filling unit individually or in combination. In particular, the described filling device can be used for filling.

[0028] The same advantages as previously described in connection with the filling unit, the filling device, and the uses are achieved. Reference is made to all statements regarding the proposed filling unit, the filling device, and the proposed uses. The method can have all the features mentioned in connection with these individually or in combination. According to a further teaching according to claim 19, which also has independent significance, a method for producing a filling unit is claimed. This is preferably designed as described.

[0029] Reference may be made to all statements relating to the proposed filling unit, the filling device, the uses and the proposed method for aseptic filling.

[0030] Claim 20 describes preferred embodiments of the method for producing the filling unit, which simplify production and improve the quality of the filling process.

[0031] In the following, the invention is explained in more detail with reference to a drawing which merely represents exemplary embodiments. In the drawing,

[0032] Fig. 1 shows a first embodiment of a proposed filling unit with a container unit,

[0033] Fig. 2 shows a second embodiment of a proposed filling unit with several container units,

[0034] Fig. 3 shows a proposed filling device with the proposed filling unit from Fig. 2 and

[0035] Fig. 4 shows a proposed use and the proposed method with a proposed filling device when filling a medium into a proposed filling unit,

[0036] Fig. 5 shows a further embodiment of a proposed filling unit with several container units.

[0037] The exemplary embodiments illustrated in the figures and thus preferred relate to proposed filling units 1. These are used here and preferably for the aseptic filling of a medium 2. This can be, in particular, a medicament and / or an active ingredient. As shown in Fig. 1, the proposed filling unit 1 has at least one container unit 3. The filling unit 1 shown in Fig. 2 has not just one, but several container units 3. The container interior 4 of the at least one container unit 3 can be sealed or can be sealed in a sterile manner.

[0038] Furthermore, the proposed filling unit 1 has a cover 5 that sterilely seals at least the container interior 4 toward the outside of the filling unit. This enables the provision of a protective cover for filling by the filling unit 1, so that a protective space no longer needs to be provided by the filling device 6 or filling system itself, but rather a protective cover can be provided by the cover 5 of the filling unit 1.

[0039] Furthermore, the filling unit 1 here has a connection 7. This serves for the sterile introduction of the medium 2 to be filled from the outside of the filling unit into the casing 5. In the exemplary embodiment, it is designed as a transfer port for the medium 2. A filling unit 8, connected or connectable to the connection 7, is then provided for filling the medium 2 introduced into the casing 5 via the connection 7 into the container interior 4.

[0040] The casing 5 of the filling unit 1 provides a sterile filling environment for the filling of the medium 2 into the container interior 4 by the filling unit 1 itself. The casing 5 protects the filling process from environmental influences, particularly from contamination by germs. It forms a protective cover.

[0041] This design allows a particularly simple and space-saving construction of the filling device 6 for filling the medium 2, since the low-germ or germ-free environment for filling can be provided by the filling unit 1 and no longer has to be provided by a part of the building, the filling system or the filling device 6.

[0042] It has also proven particularly advantageous if the filling unit 1 is designed as a single-use unit. Such a disposable design allows for high flexibility, as product changes can be carried out quickly and long preparation and cleaning times are eliminated. With the filling unit 1, after the medium 2 has been filled into the container unit 3, the container unit 3 can be sterilely sealed in the sleeve 5, and then the sleeve 5 can be opened and the sealed container unit 3 removed. By filling and sealing the container unit 3 with the sleeve 5 unopened, the risk of cross-contamination can be at least reduced, if not eliminated.

[0043] Sterile here and preferably means "sterile" as defined in the Guidelines - The Rules Governing Medicinal Products in the European Union Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 1 - Brussels, 22 August 2022.

[0044] Here and preferably, the filling unit 1 within the shell 5 and / or in the container interior 4 is sterile according to section 4.31 of the aforementioned Annex 1, preferably according to Grade B, more preferably according to Grade A.

[0045] Additionally or alternatively, the filling unit 1 within the shell 5 and / or in the container interior 4 is low in particles according to section 4.27 of the aforementioned Annex 1, preferably according to Grade B, more preferably according to Grade A.

[0046] Additionally or alternatively, the filling unit 1 and / or the interior of the casing 5 is here and preferably low in particles in the sense of the Guidance for Industry - Sterile Drug Products - Produced by Aseptic Processing - Current Good Manufacturing Practice of the US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologies Evaluation and Research (CBER), Office of Regulatory Affairs (ORA) from September 2004, Pharmaceutical CGMPs, Section IV. A Critical Area - Class 100 (ISO5).

[0047] Here and preferably, the filling unit 1 and / or the interior of the casing 5 has less than or equal to 3520 particles greater than or equal to 0.5 pm / m3 (3520 > 0.5 m / m3).

[0048] The previously described low particle content is maintained here and preferably before filling and / or during filling and / or during closing of the container unit. If the filling unit 1 is designed as a single-use unit, it preferably represents a single-use system within the meaning of the aforementioned Annex 1 or is used for filling as such.

[0049] In the exemplary embodiment, and preferably, the at least one container unit 3 comprises a container 9 and a container closure 10, by means of which the container 9 can be and / or is closed in a sterile manner within the casing 5 after filling. The container 9 can, for example, be a so-called vial, as shown in the exemplary embodiments. In particular, the container 9 can be designed as an injection vial or ampoule. It is preferably made of glass and / or plastic.

[0050] In the exemplary embodiment, the container unit 3, in particular the container closure 10, has a port 11 for piercing with a needle, through which the medium 2 can then be removed from the container 9. This allows the medium 2 to be drawn onto an injection syringe particularly easily and safely. In the exemplary embodiment, and preferably, it is provided that the port 11 remains intact after the container unit 3 has been filled with the medium 2 and closed.

[0051] Preferably, the container closure 10 is a closure that can be connected to the container 9 in a form-fitting and / or force-fitting manner. In the exemplary embodiment, it is designed as a snap-in closure. It can simply be pressed onto the container 9 after filling and then snaps into place. The container 9 is then sterilely sealed.

[0052] Alternatively, the container unit 3 can also be designed as an injection syringe, for example, as a prefillable syringe. In this case, the container 9 is preferably formed by a syringe body, and the container closure 10 by a plunger stopper of the injection syringe.

[0053] The capacity of the container unit 3 is preferably between 0.5 and 200 ml, more preferably between 0.5 and 40 ml, more preferably between 0.5 and 40 ml. As shown in Fig. 1, the filling unit 1 can have only a single container 9. However, a filling unit 1 preferably has several containers 9, as is also shown in the embodiment in Fig. 2. In particular, the filling unit 1 can have at least 2, preferably at least 10, more preferably at least 50, more preferably at least 100, more preferably at least 200, more preferably at least 500 container units 3. It then preferably has a corresponding number of containers 9 and container closures 10.

[0054] Furthermore, it is preferably provided here, as shown in Figures 1 and 2, that the sleeve 5 completely encloses the container unit 3. The sleeve 5 is at least partially made of plastic and / or at least partially flexible. Here and preferably, it is formed from plastic film. Preferably, the plastic is polyethylene (PE) and / or polycarbonate (PC) and / or polypropylene and / or perfluoroalkoxy (PFA) and / or polyetheretherketone (PEEK). The sleeve 5 is designed such that after filling with the medium 2, a sealed container unit 3 can be removed by opening the sleeve 5 while maintaining the sterility of the container interior 4. For this purpose, the container

[0055] 9 after filling in the closed shell 5 with the container closure

[0056] 10 must be closed and then the cover 5 must be opened.

[0057] In addition, a second sleeve 12 can be provided, which encloses the sleeve 5 on the outside. It serves to protect the sleeve 5 from mechanical damage. The second sleeve 12 preferably has greater mechanical strength and / or is thicker than the sleeve 5. A second sleeve 12 is optionally shown schematically in dashed lines in the embodiment of Fig. 2, but can also be provided, for example, in a filling unit 1 according to the embodiment of Fig. 1 or 5.

[0058] Furthermore, it is preferably provided here that the filling unit 1, in particular in the casing 5, has a holding device 13 for holding the at least one container 9 and / or the at least one container closure 10.

[0059] The holding device 13 serves here to hold, in particular in an aligned manner, the container 9 and the container closure 10 assigned to the container 9. As a result, the closing of the container 9 with the container closure 10 can be particularly well automated.

[0060] For this purpose, the filling unit 1 here and preferably has a container closure unit 14. This serves to receive a container closure 10 arranged separately from the container 9 and to close the container 9 with the container closure 10. This is shown in Fig. 4.

[0061] To place the container closure 10 onto the container 9, the container closure unit 14 is movable such that it can pick up the container closure 10 and place it onto the container 9. This occurs here with the sleeve 5 closed. The sleeve 5 provides the necessary flexibility for this.

[0062] The container closure unit 14 has a container closure receptacle 15 for receiving the container closure 10 inside the sleeve 5. This is preferably formed by a locking contour 16. Furthermore, the container closure unit 14 has a bellows 17. This is preferably made of silicone. It can be actuated from the outside of the filling unit to receive and release the container closure 10. This will be described in more detail in connection with the filling device 6, its use, and the method.

[0063] The filling unit 8 can, in particular, have a filling needle 18. This is guided into the container interior 4 for filling the medium 2. In a further development, the filling unit 8 can have multiple filling needles 18. For filling the medium 2, the filling unit 8, here its filling needle 18, can be moved through a container opening into the container interior 4 and / or, after filling, can be moved out of the container interior 4. This takes place with the casing 5 closed. The casing 5 provides the necessary flexibility for this.

[0064] Furthermore, it is preferably provided that the filling unit 1 has a manipulator interface 19. An end effector 20 of a manipulator 21 can engage this interface from outside the filling unit. By means of this interface, the manipulator 21 can preferably move the filling unit 8 relative to the container 9 and / or move the container closure unit 14 relative to the container 9 from outside the filling unit.

[0065] Furthermore, the manipulator 21, in particular its end effector 20, has at least one actuator 22 for actuating the container closure unit 14. In the exemplary embodiment, an actuator 22 is provided for receiving the container closure 10 and / or placing the container closure 10 onto the container 9. In the exemplary embodiment, this actuator cooperates with another actuator 23 to release the container closure 10.

[0066] The manipulator interface 19 enables a particularly simple and cost-effective design of the filling unit 1, in which the drives and the kinematics necessary for filling are provided outside the filling unit, here by the filling device 6.

[0067] Furthermore, it is preferably provided here that the manipulator interface 19 is fixedly connected to the container closure unit 14. This ensures a coupling of the movement of the manipulator interface 19 with the movement of the container closure unit 14. In the exemplary embodiment, a part of the bellows 17 of the container closure unit 14 is fixedly connected to the manipulator interface 19, while the other end of the bellows 17, which serves to receive the container closure 10, is movable relative to the manipulator interface 19. The other end of the bellows 17 can be moved relative to the manipulator interface 19 by means of a plunger 24 and the actuator 22, in particular for receiving and / or releasing the container closure 10. A counter-plunger 25 is preferably provided for releasing the container closure 10 from the container closure receptacle 15.This serves to hold down the container closure 10 when releasing the container closure 10 from the container closure receptacle 15. In the exemplary embodiment, the counter-ram 25 is in the ram.

[0068] 24 and / or adjustable against it. To move the counter-ram

[0069] 25, the further actuator 23 is provided on the manipulator 21, in particular its end effector 20.

[0070] Furthermore, it is provided here that the manipulator interface 19 is firmly connected to the filling unit 8. This couples the movement of the manipulator interface 19 with the movement of the filling unit 8. In the exemplary embodiment, the filling unit 8 and the manipulator interface 19 are designed as a single piece, here made of plastic and / or as an injection-molded part. The plastic is preferably polyethylene and / or polycarbonate.

[0071] Furthermore, it is provided here that the sleeve 5 is connected to the manipulator interface 19, in particular by a material bond. In the exemplary embodiment, these are welded together. In the exemplary embodiment, the sleeve 5, as shown in the figures, is designed to be flexible at least in the area around the manipulator interface 19 and / or is designed as a plastic film in the area around the manipulator interface 19. This enables relative movement of the manipulator interface 19, in particular including the filling unit 8 and / or the container closure unit 14, relative to the at least one container 9 of the filling unit 1.

[0072] Preferably, the filling unit 8 and / or the container closure unit 14 are movable relative to the containers 9 such that filling into all containers 9 and / or their closure with the container closures 10 is possible. The necessary flexibility is provided by the sleeve 5.

[0073] Particularly for the filling of medications and / or active ingredients, it can be advantageous if the filling unit 1 has a sterility indicator 26, by means of which the maintenance of a sterile environment during filling can be checked. This can be, for example, a Petri dish and / or a container 9 with nutrient medium. Furthermore, the filling unit 1 can have a sampling unit 27, in particular a rod. Such a rod is indicated in dashed lines in Fig. 2b). With this, samples can be taken and fed to the sterility indicator 26. Preferably, the sampling unit 27 is connected to the manipulator interface 19, in particular permanently connected, or can be connected for sampling.

[0074] In particular, the sterility indicator 26 and / or the sample unit 27 can also be held in the holding device 13. For example, it can be formed by a container 9, in particular a vial. This can then be filled with a nutrient medium.

[0075] Additionally or alternatively, the filling unit 1, particularly in its casing 5, can have a sterilization indicator 43. The sterilization indicator 43 can be used to indicate that the filling unit has been sterilized. For example, it can be provided that the indicator has a display indicating sterilization of the filling unit, for example, as shown by way of example in Fig. 5, the display changes color during sterilization of the filling unit 1 or the sterilization is indicated in another way by the sterilization indicator 43. In the exemplary embodiment, and preferably, the connection 7 is an aseptic connection 28. Such aseptic connections 28 are known from the prior art, particularly for connecting tubes 29 from the laboratory sector, and are also referred to as "aseptic connectors." They allow sterile fluid transfer.These are sold by various manufacturers under different brand names such as AseptiQuik, MicroCNX, Kleenpak or Opta in different designs.

[0076] Furthermore, the filling unit 1 can have a pipe and / or a hose 29 for connecting the filling unit 8 to a reservoir 30 provided outside the filling unit containing the medium 2 to be filled. Here and preferably, the connection 7 is formed at a hose end 29. In the exemplary embodiment, by the aseptic connection 28. The connection 7 here is preferably a force-fitting and / or form-fitting connection 7. However, it can also be provided as a material-fit connection 7 to the reservoir 30.

[0077] Here, and preferably, the hose 29 does not extend through the casing 5 and / or the casing 5 is designed without loops on its interior. Here, and preferably, the hose 29 is connected to the filling unit 8 outside the casing 5.

[0078] Aseptic connectors 28 can be designed as single-use connectors. In this case, they allow for the creation of a sterile connection only once. However, there are also multi-use connectors that can be separated and reconnected sterilely. Such multi-use connectors are generally resealable.

[0079] For example, the aseptic connection 28 can have a pull tab, by removing which a fluid connection can be established after the connection of the connection 7 with its mating connection.

[0080] Both the provision of an aseptic connection 28 and, additionally or alternatively, a hose 29 for connecting the connection 7 to the filling unit 8 enables a particularly simple and flexible connection of the filling unit 1 to a storage unit 30 containing the medium 2 to be filled.

[0081] The connection 7 can have a filter 31 for filtering the medium 2 conveyed through it. Here and preferably, the casing 5 is designed to be essentially gas-tight. Only the connection 7 and, if present, a gas port 32 allow gas to pass from the outside of the filling unit into the casing 5. The filling unit 1 can have a gas port 32, in particular with a gas port filter 33, for pumping gas into the filling unit 1, in particular into its casing 5, and / or for discharging gas from the filling unit 1, in particular from its casing 5. The gas port 32 is preferably connected to the filling unit 1 via a gas port hose 34. Two gas ports 32 can also be provided, with one then preferably serving as a gas inlet and the other as a gas outlet.

[0082] Alternatively or in addition to a gas port 32, it can also be provided that a gas is pumped into or discharged from the filling unit 1 via the connection 7. This enables the casing 5 to be inflated. An integrity test of the filling unit 1 can be performed. In the exemplary embodiment, the integrity test is an integrity test of the casing 5 of the filling unit 1 before and / or after filling. In principle, however, such a test can also be performed additionally or alternatively during filling.

[0083] Furthermore, the filling unit 1 can have a container handling unit 35 for picking up and placing a container 9, in particular a vial, in the filling device 1. This unit can be used to move the container 9 within the filling unit 1. In contrast to the illustration in Fig. 2a), such a container handling unit 35 is indicated in dashed lines in Fig. 2b). With it, a container 9 can be removed from the holding device 13 and reinserted into the holding device 13, in particular at a different location.

[0084] Also proposed is a filling device 6 for filling, in particular aseptically, a medium 2 into a filling unit 1. This is shown in Fig. 3. The filling device 6 has a reservoir 30 and / or a reservoir holder 36. This allows the medium 2 to be filled to be made available outside the filling unit 1. Furthermore, the filling device 6 has a conveyor device 37 for conveying the medium 2 to be filled into a filling unit 1. This is preferably designed as previously described. It can have the described features individually or in combination. In the exemplary embodiment in Fig. 3, the reservoir holder 36 carries a reservoir 30 with the medium 2 to be filled. In the exemplary embodiment, the reservoir 30 is designed as a plastic bag. It is a single-use reservoir. It has a reservoir connection 38. This is designed here as an aseptic connection 28.The storage connection 38 is connected to the connection 7 of the filling unit 1 for filling. This creates an aseptic connection. In the exemplary embodiment, the storage connection 38 is formed at one end of a storage hose 39 of the storage unit 30. This enables particularly simple connection of the filling unit 1 to the storage unit 30. The storage connection 38 and the connection 7 of the filling unit 1 are connected here, preferably with a force-fitting and / or form-fitting connection. Additionally or alternatively, the storage connection 38 and the connection 7 of the filling unit 1 can also be connected with a material fit.

[0085] The conveying device 37 for conveying the medium 2 to be filled into a filling unit 1 is designed here as a pump, in particular as a peristaltic pump. It is designed here as a hose pump, which pushes the medium 2 to be conveyed through the hose 29 by external mechanical deformation of the latter. In the exemplary embodiment and preferably, the conveying device 37 for conveying acts on the hose 29 of the filling unit 1. Additionally or alternatively, however, it can also be provided that it acts on the storage hose 39 of the reservoir 30. It is arranged here outside the filling unit 1. The conveying device 37 is arranged, as shown in Fig. 3, in the filling device 6 above the filling unit 1 and / or below the reservoir 30.

[0086] Furthermore, the filling device 6 has a manipulator 21 for filling the medium 2 into the at least one container 9. This manipulator is arranged outside the filling unit 1. It engages the manipulator interface 19 of the filling unit 1 for filling the medium 2 into the containers 9 and / or for closing the containers 9. This is shown in an enlarged view in Fig. 3.

[0087] The manipulator 21 is preferably a robot with at least two, preferably at least three, axes of movement. In particular, the robot can have at least two, preferably three, rotary axes and / or at least two, preferably at least three translational axes. In the exemplary embodiment, the robot is designed as a SCARA robot. However, it can also be designed as an industrial robot, in particular a five-axis or six-axis industrial robot, or as a gantry robot.

[0088] In the exemplary embodiment, the filling device 6 further comprises a gas conveying device 40, in particular a gas pump 41. This is arranged outside the filling unit 1. In the exemplary embodiment, the gas conveying device 40 is connected to a gas port 32 of the filling unit 1. Alternatively, however, it can also be connected to the connection 7. It serves to introduce and / or remove gas, in particular air, into or from the filling unit 1. Preferably, germ-free air is pumped into the casing 5 of the filling unit 1. To ensure this, appropriate air filters are provided. Here and preferably, the gas port 32 of the filling unit 1 has corresponding gas port filters 33. Additionally or alternatively, the gas conveying device 40 can also be used to create a protective atmosphere in the casing 5 of the filling device 6.

[0089] In addition, the filling device 6 can have a weighing unit 42. The weighing unit 42 can be used to check the amount of medium 2 filled into the individual containers 9 of the filling unit 1. Provision can be made for the filling unit 1 to be arranged on the weighing unit 42, and / or for the containers 9 to be brought to the weighing unit 42 individually or in groups, for example, by means of the manipulator 21 and the container handling unit 35. Preferably, a container 9 is weighed before and / or during and / or after filling.

[0090] In the exemplary embodiment, the filling unit 1, here the manipulator 21, in particular its end effector 20, has a container closure unit 14. This will be described in more detail in connection with the method.

[0091] The use of a filling unit 1 for aseptically filling a medium 2, in particular a medicament, into at least one container unit 3 is also proposed.

[0092] Reference is made to all statements regarding the proposed filling unit 1 and the proposed filling device 6. Furthermore, the use of a sleeve 5 made at least partially of plastic and / or at least partially flexible as a protective cover, in particular for providing a sterile space, during the aseptic filling of a medium 2, in particular a medicament and / or active ingredient, into a container 9 and / or during the closing of the container 9, in particular with a container closure 10, after filling the container 9, is proposed. The sleeve 5 protects the filling process into the container 9. It at least seals off the container interior 4 in a sterile manner to the outside.

[0093] Preferably, the sleeve 5 is designed as a sleeve 5 of a filling unit 1, which has the container 9. For this, the filling unit 1 can also have a container closure 10. These preferably form a previously described container unit 3. Regarding the design of the filling unit 1 as a whole and the sleeve 5 in particular, reference is made to the descriptions of the filling unit 1, the filling device 6, and the above-mentioned use.

[0094] The casing 5 can be used, in particular as a single-use casing, for the aseptic filling of the medium 2 into at least one, preferably the majority, more preferably all, containers 9 at least partially accommodated therein.

[0095] As described, the medium 2 to be filled is preferably provided from outside the casing 5 for filling, in particular through a fluid line, here the storage hose 39.

[0096] A method is proposed for the, in particular aseptic, filling of a medium 2, in particular a medicament, into a container unit 3 of a filling unit 1, in particular according to one of claims 1 to 12, wherein the filling unit 1 has at least one container unit 3, the container interior 4 of which can be closed or is closed in a sterile manner, a sleeve 5, comprising the following steps:

[0097] - connecting a storage device 30 containing the medium 2 to be filled to the filling unit 1, in particular to a connection 7 of the filling unit 1,

[0098] - Introducing the medium 2 into the casing 5 and filling the medium 2 by means of the filling unit 8 into the container interior 4 of the at least one container unit 3. Reference may be made to all statements regarding the proposed filling unit 1, the filling device 6 and the proposed uses.

[0099] For filling, the filling unit 1 is preferably first connected in or to the filling device 6. The reservoir 30 is connected to port 7. The gas delivery device 40 is connected to the gas port 32. The hose 29 is inserted into the peristaltic pump.

[0100] Preferably, gas, in this case ambient air, is then pumped into the filling unit 1, in this case the casing 5 of the filling unit 1. In this way, an integrity test can be performed. A pressure test is performed to check whether the casing 5 is leak-tight. Since the gas is filtered before being pumped into the casing 5, sterility is maintained. In the exemplary embodiment, gas is vented from the casing 5 before filling begins.

[0101] Particularly preferably, the integrity test of the filling unit 1, in particular of the casing 5 of the filling unit 1, is performed before connecting a reservoir 30 and / or before fluidically connecting a reservoir 30 to the filling unit 1. In particular, the integrity test can be performed after connecting the manipulator 21 to the filling unit 1.

[0102] The container(s) 9 can then be filled with the medium 2. This is shown in Fig. 4. For this purpose, the filling unit 8 is guided to the container 9 to be filled. This is done here by the manipulator 21. The filling needle 18 is inserted into the container 9, as shown in Fig. 4a). The medium 2 can then be filled into the container 9. It is conveyed by the conveyor device 37 into the container interior 4. After this and / or during filling, the filling needle 18 is guided out of the container 9 again. This movement is effected by the manipulator 21. The flexibility of the sleeve 5 makes these movements of the filling unit 8 relative to the container 9 or containers 9 very easy. After one container 9 has been filled, the next container 9 of the filling unit 1 can be filled, or the container 9 can first be closed with the container closure 10.

[0103] It is particularly noteworthy that the filling unit 1 is preferably designed without actuators. All actuators required for filling and / or closing the containers 9 are provided here, preferably separately from the filling unit 1, in particular on the manipulator 21.

[0104] In the exemplary embodiment, the container closure 10 is received by the container closure unit 14, in particular in a force-fitting and / or form-fitting manner. A plunger 24 and / or a counter-plunger 25 can be provided to release the container closure 10 from the container closure unit 14, in particular after a container 9 has been closed with the container closure 10. In the exemplary embodiment, an actuator 22, 23 or one actuator each 22, 23 is preferably provided to move the plunger 24 and / or counter-plunger 25 on the manipulator 21, in particular its end effector 20.

[0105] The closing of the container 9 is shown in Figures 4c) and 4d). The container closure unit 14 receives the container closure 10. To do this, the manipulator 21 presses the bellows 17 onto the container closure 10 with a plunger 24. This receives the container closure 10. The container closure 10 can then be placed onto the filled container 9 with the container closure unit 14, and the container can be closed. In the exemplary embodiment, this is a snap closure. The container closure 10 can alternatively be crimped or glued. In this case, the container unit 3 is sealed in a sterile manner. By lifting the container closure unit 14, the container closure 10 can then be released. Additionally or alternatively, the container closure 10 can be released using the plunger 24 and the counter-plunger 25. For this purpose, the plunger 24 is lifted by the actuator 22 and the counter-plunger 25 is pressed onto the container closure 10 by means of the further actuator 23.This allows the container closure 10 to be released from the locking contour 16 of the container closure unit 14. For example, the release can be achieved by pulling using the plunger 24 and / or by pressing, in particular on the bellows 17, using the counter-plunger 25. The container unit 3 is then properly and sterilely sealed.

[0106] The next container 9 can be filled and / or the next container 9 can be closed. This is preferably done as previously described.

[0107] After the containers 9 have been filled, a further integrity test can be performed. For this purpose, the casing 5 is subjected to a pressure test, preferably by the gas delivery device 40. The integrity of the casing 5 is tested here, and preferably, in particular before and / or after the medium 2 is poured into the container interior 4. In the exemplary embodiment, the casing 5 is subjected to a pressure test for this purpose. During this test, an excess pressure relative to the ambient pressure is generated in the casing 5, and it is checked whether the pressure is maintained.

[0108] By filling and subsequently closing the container unit 3 or the container units 3 in the intact and / or unopened sleeve 5, the risk of contamination can be significantly reduced.

[0109] A method for producing a filling unit 1 is also proposed. This is preferably designed as described. The method comprises the step of inserting the at least one container unit 3 into the casing 5 and subsequently closing the casing 5, in particular by welding.

[0110] Reference may be made to all statements relating to the filling unit 1, the filling device 6, the uses and the filling method.

[0111] During the manufacture of the filling unit 1, it is preferably provided that at least a part of the casing 5 is provided with the connection 7 and / or the filling unit 8. For example, these can be welded to the casing 5. Furthermore, it is provided that the filling unit 1 is sterilized, in particular after closing. Sterilization is preferably carried out by means of radiation, in particular X-rays and / or gamma radiation and / or electron beam irradiation. Alternatively or additionally, sterilization can also be carried out by means of another sterilization method, for example steam sterilization and / or ethylene oxide sterilization. Additionally or alternatively, the components of the filling unit 1 can be pre-sterilized and the filling unit 1 can be manufactured in a sterile manner.

[0112] Finally, the embodiment of Fig. 5 will be briefly described. The filling unit 1 is essentially designed like the filling units 1 previously described in connection with Figs. 1 to 4. It can have the features described in connection with the previous embodiments individually or in combination.

[0113] The filling unit of Fig. 5 here and preferably additionally has a sterilization indicator 43. Here and preferably, the containers 9 and the container closures 10 are preferably arranged stationary in the holding device 13.

[0114] Here, and preferably, all containers 9 and / or all container closures 10 can be approached by the manipulator interface 19 and / or the filling unit 8 and / or the container closure unit 14 for filling and closing by means of the manipulator 21. They can be approached without adjusting the holding device 13. The sleeve 5 provides sufficient flexibility for this.

[0115] Furthermore, the container closure unit 14 of the filling unit 1 can be designed without bellows. Accordingly, it can additionally or alternatively be provided that the locking contour 16 of the container closure unit 14 is designed to be substantially fixed to the manipulator interface 19. "Substantially" here and preferably means that the locking contour 16 can still perform the necessary movements for receiving and releasing a container closure 10. A plunger 24 and / or counter-plunger 25 is also preferably provided here for release. This is / are here and preferably not a component of the filling unit 1, but rather preferably a component of the manipulator 21, in particular its end effector 20.

[0116] Preferably, the manipulator interface 19 and / or the container closure unit 10 and / or the filling unit 8, as shown in the figures, are arranged on an upper side of the casing 5.

[0117] The figures further show that the manipulator interface 19 and / or the container closure unit 14 and / or the filling unit 8, in particular in the case of a fully expanded casing 5, is / are arranged above, preferably over, the containers 0 and / or container closures 10.

[0118] In addition, it can be provided that the manipulator interface 19 and / or the container closure unit 14 and / or the filling unit 8 is / are arranged above the containers 9 and / or container closures 10 when the casing 5 is contracted by sucking off the gas from the filling unit 1, in particular in the delivery state before connection to the filling device 6. As shown in Figures 1 to 4, the gas port 32 can be connected to the manipulator interface, in particular via a gas port hose 34. Additionally or alternatively, a gas port 32 can be connected separately from the manipulator interface 19 to the filling unit, in particular to the preferably flexible casing 5, in particular via a gas port hose 34, as shown in Figure 5. Preferably, a gas introduced into the filling unit 1 via the gas port 32 flows into the casing 5 from below, in particular from a bottom side, as shown in Fig. 5.The described embodiments make it possible to provide a protective cover by the filling unit 1 itself when filling a medium 2, so that this no longer needs to be provided by a filling system or filling device 6. This enables simple, safe, and cost-effective filling of a medium 2, especially with small batches and / or frequent medication changes.

[0119] List of reference symbols

[0120] 1 filling unit

[0121] 2 Medium

[0122] 3 container unit

[0123] 4 Container interior

[0124] 5 Cover

[0125] 6 Filling device

[0126] 7 Connection

[0127] 8 filling unit

[0128] 9 containers

[0129] 10 Container closure

[0130] 11 ports

[0131] 12 second shell

[0132] 13 Holding device

[0133] 14 Container closure unit

[0134] 15 Container closure holder

[0135] 16 locking contour

[0136] 17 bellows

[0137] 18 Filling needle

[0138] 19 Manipulator interface

[0139] 20 End effector

[0140] 21 Manipulator

[0141] 22 Actuator

[0142] 23 additional actuators

[0143] 24 tappets

[0144] 25 counter tappets

[0145] 26 Sterility indicator

[0146] 27 sample units

[0147] 28 aseptic connection

[0148] 29 hose

[0149] 30 storage

[0150] 31 filters

[0151] 32 Gasport

[0152] 33 Gasport filters

[0153] 34 Gas port hose

[0154] 35 Container handling unit 36 ​​Storage holder

[0155] 37 conveyor system

[0156] 38 memory connection

[0157] 39 Storage hose 40 Gas delivery device

[0158] 41 Gas pump

[0159] 42 weighing unit

[0160] 43 Sterilization indicator

Claims

Patent claims 1. Filling unit for the, in particular aseptic, filling of a medium (2), in particular a medicament, with at least one container unit (3), the container interior (4) of which can be closed or is closed in a sterile manner, with a sleeve (5) which closes at least the container interior (4) in a sterile manner towards the outside of the filling unit, with a connection (7) for the sterile introduction of the medium (2) to be filled from the outside of the filling unit into the sleeve (5) and with a filling unit (8) which is connected or connectable to the connection (7) and for filling the medium (2) introduced into the sleeve (5) via the connection (7) into the container interior (4).

2. Filling unit according to claim 1, characterized in that the at least one container unit (3) has a container (9), in particular a vial, and a container closure (10), in particular a vial cap, by means of which the container (9) can be closed and / or is closed in a sterile manner after filling, in particular within the sleeve (5), preferably in that the container closure (10) is a closure, in particular a snap closure, which can be connected to the container (9) in a form-fitting and / or force-fitting manner.

3. Filling unit according to claim 1 or 2, characterized in that the sleeve (5) completely encloses the container unit (3), and / or that the sleeve (5) is at least partly made of plastic and / or is at least partly designed to be flexible.

4. Filling unit according to one of the preceding claims, characterized in that the filling unit (1), in particular in the casing (5), has a holding device (13) for holding the at least one container (9) and / or the at least one container closure (10), preferably that the holding device (13) holds the container (9) and the container closure (10) associated with the container (9) aligned with one another.

5. Filling unit according to one of the preceding claims, characterized in that it comprises a container closure unit (14) for receiving a container closure (10) arranged separately from the container (9) and for closing the container (9) with the container closure (10).

6. Filling unit according to one of the preceding claims, characterized in that the filling unit (1) has a manipulator interface (19) to which an end effector (20) of a manipulator (21) can engage from the outside of the filling unit and by means of which the latter can move the filling unit (8) relative to the container (9) and / or move the container closure unit (14) relative to the container (9).

7. Filling unit according to one of the preceding claims, characterized in that the manipulator interface (19) is firmly connected to the container closure unit (14) and / or the filling unit (8) and / or the sleeve (5).

8. Filling unit according to one of the preceding claims, characterized in that the sleeve (5) is designed to be flexible at least in the area around the manipulator interface (19) and / or is designed as a plastic film in the area around the manipulator interface (19).

9. Filling unit according to one of the preceding claims, characterized in that the filling unit (1) has a sterility indicator (26), in particular a Petri dish and / or a container (9) with nutrient medium, by means of which the maintenance of a sterile environment during filling can be checked.

10. Filling unit according to one of the preceding claims, characterized in that the connection (7) is an aseptic connection (28) and / or that the filling unit (1) has a pipe and / or a hose (29) for connecting (7) the filling unit (8) to a storage (30).

11. Filling unit according to one of the preceding claims, characterized in that the filling unit (1) has a gas port (32), in particular with a gas port filter (33), for pumping gas into the filling unit (1) and / or for discharging gas from the filling unit (1).

12. Filling device for, in particular aseptic filling, of a medium (2) into a filling unit (1) with a storage (30) or a storage holder (36) for the medium (2) to be filled outside the filling unit (1) and with a conveyor device (37) for conveying the medium (2) to be filled into the Filling unit (1), preferably that the filling unit (1) is designed according to one of the preceding claims.

13. Use of a filling unit (1) according to one of claims 1 to 11 for the aseptic filling of a medium (2), in particular a medicament, into at least one container unit (3).

14. Use of a sleeve (5) consisting at least partly of plastic and / or at least partly pliable as a protective cover, in particular for providing a sterile space during a, in particular aseptic, filling of a medium (2), in particular a medicament, into a container (9) and / or during the closing of the container (9) after filling the container (9).

15. Use according to claim 14, characterized in that the casing (5), in particular as a single-use casing, is used for the aseptic filling of the medium (2) into at least one, preferably the majority, more preferably all, containers (9) at least partially received therein.

16. Use according to claim 14 or 15, characterized in that the medium (2) to be filled is provided from outside the casing (5) for filling, in particular through a fluid line.

17. A method for, in particular aseptically, filling a medium (2), in particular a medicament, into a container unit (3) of a filling unit (1), in particular according to one of claims 1 to 12, wherein the filling unit (1) has at least one container unit (3), the container interior (4) of which is sterilely sealable or sealed, and a sleeve (5), comprising the following steps: - Connecting a storage device (30) containing the medium (2) to be filled to the filling unit (1), in particular to a connection (7) of the filling unit (1). - introducing the medium (2) into the casing (5) and filling the medium (2) by means of the filling unit (8) into the container interior (4) of the at least one container unit (3).

18. Method according to claim 17, characterized in that the integrity of the casing (5), in particular before and / or after filling the medium (2) into the container interior (4), is checked, preferably that the casing (5) is subjected to a pressure test for this purpose.

19. Method for producing a filling unit (1) for, in particular aseptically, filling a medium (2), in particular a medicament, with at least one container unit (3), the container interior (4) of which is or can be closed in a sterile manner, and with a sleeve (5) which at least closes the container interior (4) in a sterile manner towards the outside of the filling unit, with a connection (7) for the sterile introduction of the medium (2) to be filled from the outside of the filling unit into the sleeve (5) and with a filling unit (8) which is connected or connectable to the connection (7) for filling the medium (2) introduced into the sleeve (5) via the connection (7) into the container interior (4), comprising - the introduction of at least one container unit (3) into the casing (5) and - then closing the casing (5), in particular by welding.

20. Method according to claim 19, characterized in that at least a part of the casing (5) is provided with the connection (7) and / or the filling unit (8), and / or that the filling unit (1), in particular after closing, is sterilized, in particular by means of radiation, preferably gamma radiation and / or electron irradiation.

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