METHOD AND APPARATUS FOR STERILE OR ASEPTIC HANDLING OF CONTAINERS

Abstract

The invention relates to a device and a method for the sterile or aseptic handing of containers, which method includes at least the following process step of: evaluating whether a container is safely closed by means of a stopper by determining whether an expected low pressure, preferably a vacuum, is present in the interior of the container.

Description

PRIOR ART

The invention is based on a method and an apparatus for sterile or aseptic handling of containers as generically defined by the preambles to the independent claims. From European Patent Disclosure EP 1 447 328 B1, a method for sterile metering of vials is already known. After the vial and cap have been put together, they are rinsed. Next, a protector is placed thereon. In an autoclave, the arrangement is sterilized. After cooling and removal of the protector and cap, the liquid is dispensed into the vial. Next, the vial is closed again. The filling is recorded with a video camera for purposes of documentation. After the encapsulation, the vial is provided, by means of a laser beam, with identification that says when the metering was done.

It is the object of the present invention to reduce the number of handling steps, especially in the time prior to the filling operation. This object is attained by the characteristics of the independent claims.

Advantages of the Invention

Methods and apparatuses according to the invention for sterile handling of containers are distinguished in that it is checked whether a container is safely closed with a stopper by ascertaining whether an expected underpressure, preferably a vacuum, is still present in the interior of the container. Thus the combination of the container closed with a stopper is sterilized and also delivered in this combination for filling. This avoids having to deliver the stoppers for closure separately along with the necessary sterilization processes. Moreover, the check for integrity ensures that the delivered containers with stoppers meet the sterility requirements, since the containers are properly closed, and in every case the interior thereof still meets the sterility requirements. This concept also makes it possible for the stopper, which is to be removed in the filling process, to be used, preferably by the same handling device, for closure after the filling has been done. A device for supplying stoppers separately can also be dispensed with. Preferably, the manipulator, such as a gripper device, which must be provided in any case for stopper removal, is used for closing the filled container as well. As a result, the costs for the system can be reduced still further.

In an expedient refinement, it is provided that the checking of the expected underpressure is effected on the basis of a force measurement of that particular force that is necessary for removing the stopper from the container. A corresponding force-measuring device can be provided, or is already present, on the stopper removal device, such as a manipulator. The force is a measure for whether the interior of the container is still subjected to the expected underpressure, which allows the conclusion to be drawn that the container and stopper arrangement is safe. If underpressure is still present, the force that must be exerted to remove the stopper is significantly greater than would be the case with a damaged container and stopper connection with an associated pressure equilibrium in the interior. Thus the force is a good indicator of the integrity of the arrangement of the container with the stopper. Since the manipulator, to remove the stopper, must necessarily come into mechanical contact with the stopper anyway, force measurement is also easy to achieve.

In an expedient refinement, it is provided that the checking of the expected underpressure is effected optically. To that end, a laser beam is preferably shone through the container. On the basis of the optical spectrum of the radiation arriving on the other side, conclusions can be drawn about the medium located in the container or about pressure conditions in the interior of the container. In the case of underpressure, an altered spectrum must be expected, compared to what would be the case at ambient pressure, or in other words in the situation where a stopper is no longer properly seated. Such optical checking devices can be installed without major additional expense and are known in principle.

In an expedient refinement, it is provided that a plurality of closed containers are placed in at least one tray. The containers located in the tray, closed with stoppers and with an underpressure applied in the interior, are subsequently sterilized. The sterilization can be done for instance by the manufacturer of the containers and stoppers. However, it would also be conceivable to do the sterilization directly before filling. Handling by means of trays simplifies the transporting and delivery of the containers to downstream process steps.

In an expedient refinement, it is provided that the checking whether the container is safely closed with a stopper is done under clean room conditions. It can thus be ensured that when the stopper is removed for checking or for ensuing filling of the container, re-sterilization of the container need no longer be done. As a result, the number of required steps for sterilizing the containers is reduced.

Further expedient refinements will become apparent from further dependent claims and from the specification.

DRAWINGS

One exemplary embodiment of the method and of the apparatus for sterile handling of containers is shown in the drawings and will be described in further detail below.

FIG. 1 schematically shows the three process steps, from closing the containers to their sterilization;

FIG. 2 shows the process steps, from checking whether the container is safely closed with a stopper to the closure of the filled containers;

FIG. 3 shows the checking of the underpressure by means of optical methods;

FIG. 4 shows the checking of the underpressure by means of mechanical force measurement; and

FIG. 5 shows a bar gripper for the removal or placement of a plurality of stoppers.

In a vacuum chamber 14, a stopper 12 is placed on a container 10 by a stopper closure device 16 and closed with the application of an underpressure. Thus an underpressure is created in the interior of the container 10 as well. The containers 10 thus closed at underpressure, preferably a vacuum, are then placed in trays 18 by a gripper device 19, so that now a plurality of containers 10, closed with stoppers 12, are positioned in a tray 18. This tray 18, with the containers 10 disposed in it, proceeds into a sterilizer 12, in which the containers 10 are sterilized. Next, the trays 18 are provided with a surrounding packaging as protection during shipping.

The thus-sterilized containers 10 are then brought into a clean room 22, in which a plurality of stations are disposed. One of these is a testing unit 24. This unit 24 checks whether the expected underpressure prevails in the interior of the still-closed container 10, as an indicator for an intact container that is still properly closed with the stopper 12. As part of a stopper removal device 26, a suitable manipulator or gripper device 44 removes the stopper 12. Next, the opened container 10—if it was recognized as being properly closed—is filled in a filling machine 28. Optionally, filled containers 10 can be subjected to an internal process control 30, which ascertains whether the container 10 has been filled with the correct quantity of liquid. In a closing station 32, which can also be a component of the filling machine 28, the filled container 10 is re-closed with the stopper 12.

In FIG. 3, the checking is done as to whether the container is safely closed with a stopper. To that end, a laser 36 shines through the preferably transparent container 10. The radiation passing through the container 10 is detected on the other side by an optical receiver 38. The properties of the detected radiation provide information as to whether an expected underpressure still prevails in the interior of the container 10. It can thus be told whether the container 10 is still safely closed with the stopper 12.

In an alternative embodiment of the testing unit 24, a gripper device 44 is now provided with a gripper 42, which serves to remove the stopper 12 from the container 10. The gripper device 44 is furthermore provided with a force-measuring device 46, which ascertains a measure for the pressure required for removing the stopper 12. From the pressure detected, it is recognized whether the expected underpressure still prevails in the interior of the container 10, or whether the container 10 is no longer properly closed. Upon the application of an underpressure or vacuum in the interior of the container 10, a significantly greater force is required for removing the stopper 12, which thus provides information as to the safeness of the closure of the container 10 with the stopper 12. The container 10 is provided on its underside with a flange 40, which cooperates with a retaining device, not shown, for exerting a contrary force for removing the stopper 12.

FIG. 5 shows the top view on a bar gripper 48 that has a plurality of openings for receiving a plurality of stoppers 12.

The devices shown in the drawings function as follows: The containers 10 are filled, preferably in the pharmaceutical field with medications, under aseptic conditions and then re-closed with the stoppers 12. The containers 10 may for instance be vials or bottles made of glass or plastic, or the like. The liquid pharmaceuticals dispensed into the containers 10 are removed in the hospital or the doctor's office, for instance by piercing the stopper 12 with an injection needle. The stopper 12 is equipped accordingly for that purpose.

To reduce the number of sterilization steps in the time before the filling of the containers 10, it is now proposed that in a first step, the container 10 and the stopper 12 are closed. This can be done for instance at the manufacturer of the containers 10 and/or stoppers 12. In the ensuing sterilization step, in order to tell reliably that the container 10 is still properly closed by the stopper 12 and that the closure is intact before further processing, an underpressure, preferably a vacuum, is generated in the interior of the container 10. This is done in the vacuum chamber 14, in which the container 10 is closed with a stopper 12 by means of the stopper closure device 16. The stopper closure device 16 may for instance be a manipulator, that is, a robot with a gripper. Under some circumstances, it could be provided that a protector be disposed over the stopper 12, which protects the stopper 12 for the further handling processes. However, this protector is not absolutely necessary.

In a further step, the various closed containers 10 are delivered by the gripper device 19 to a tray 18. The tray 18 has receptacles and openings that are adapted to the outer diameter of the container 10, so that a plurality of these containers 10 can be received in the tray 18 and thus can be delivered simultaneously to the further processing operations. Although this so-called preformatting is helpful for further handling, it is not absolutely necessary.

The tray 18 thus equipped with containers 10 is now delivered to a sterilizer 20. The underpressure or vacuum continues to exist in the interior of the containers 10, as long as the closures remain safe; that is, as long as the stopper 12 correctly closes the container 10 so that the underpressure cannot escape. The sterilizer 20 employs conventional sterilizing methods, based for instance on radiation sterilization (for instance with gamma rays), heat generation, for instance by means of plasma, or electron beams, or the like. The sterilizer 20 could be effected either inline, that is, in the context of the filling process and thus in the vicinity of the filling machine 28. However, the sterilizer 20 could equally be located spatially separately from the filling machine 28, for instance at specialized companies that perform the sterilization of the container 10 with the stopper 12 placed on it using underpressure prevailing in the interior of the container. By means of the sterilization process, the interior of the container 10 is sterilized as well. In the case of a sterilizer 20 located remotely from the filling machine 28, the tray 18 could be packaged accordingly for being transported to the filling machine 28 under sterile conditions.

Once the sterilization has been done, the closed containers 10 enter the clean room 22. Before that, any packaging that may have been present around the containers 10 or the trays 18 is removed. Containers 10 disposed on the tray 18 could also be separated again. Alternatively, the containers 10 could be delivered to the clean room 22 while still disposed on the tray 18.

The testing unit 24 is located in the clean room 22. However, it could also be disposed in a separate clean room that is separate from that of the filling machine 28. The testing unit 24 ascertains whether the stopper 12 is still properly closing the container 10. This is ascertained from indicators of the pressure conditions in the interior of the container 10. If the stopper 12 is still properly closing the container 10, then an underpressure or vacuum still prevails in the interior. However, in the event of a defect, the interior as well will be exposed to ambient pressure. Different versions of the testing unit 24 will be described hereinafter in conjunction with FIGS. 3 and 4. Containers 10 in which an expected underpressure does not prevail in the interior are removed and not filled, since they do not meet the sterility requirements.

In the case of containers 10 that are intact—the expected underpressure still prevails in the interior—the various stoppers 12 are removed. This can be done for instance by means of the gripper device 44 that is also disposed in the clean room 22. The opened container 10 is now filled with the desired quantity of the desired liquid in the desired quantity in the filling machine. In an internal process control 30, the desired filling quantity is monitored, and if deviations occur, corrective procedures are initiated. To that end, the weight or the fill level of the filled container 10 is for instance ascertained, for instance by means of X-radiation or optically.

Next, in the closing station 32, the corresponding stopper 12 is placed back on the filled container 10. For that purpose, the same gripper device 44 could preferably hold the removed stopper 12 during the filling operation and then place it back on again in the context of the closure operation. This would eliminate a separate stopper delivery. A pick-and-place device could be provided as the gripper device 44. Before closure with the stopper 12, freeze drying might possibly be necessary, to remove condensate from the container 10.

Next, the closed container 10 is transported onward to a cap placement station, which places a cap as well on the container 10 that is closed with the stopper 12 and connects the cap to the container 10, for instance by means of crimping. Suitable marking of the container 10 with regard to production information or the like, for instance by means of lasers, can then ensue as well.

The testing unit 24 can employ arbitrary physical principles, which are suitable for performing underpressure detection or vacuum detection in the interior of the container 10. For example, optical methods are suitable, if a laser 36 shines through the interior of the container 10. The arriving radiation is detected by a receiver 38. From the frequency spectrum, it can for instance be found whether a vacuum prevails in the interior of the container 10, or not. For instance, the optical absorption behavior in a vacuum is different from what it is at ambient pressure. It would also be possible to dispose the receiver 38 on the same side as the laser 36 and to divert the radiation that passes through the interior to the receiver 38 by means of a reflector.

Another advantageous embodiment of the testing unit 24 is shown in FIG. 4. For filling the container 10, the stopper 12 must be removed anyway. This is done by the gripper device 44. This gripper device 44 can now be additionally equipped with a force-measuring device 46, or the force-measuring device is present anyway in the case of a robot arm. Based on the force that is necessary for removing the stopper 12 from the container 10, conclusions can be drawn about the pressure conditions that prevail in the interior of the container 10. For instance, a significantly increased expenditure of force is necessary to remove the stopper 12 from the container 10 in the presence of underpressure or vacuum than is the case with ambient pressure. The detected force is compared with a limit value. If the force is below the limit value, this is an indication of a container 10 that is no longer intact, since given the force detected, everything points to a broken vacuum.

To facilitate the removal of the stopper 12, the container 10 is provided on its lower edge with a securing flange 40 annularly surrounding that edge. The upper side of the securing flange 40 is surrounded by a fixed retaining device 50, so that the container 10 upon removal of the stopper 12 cannot be moved upward as well along with the stopper. The gripper device 44 may also be embodied as a bar gripper 48. Then it becomes possible to remove a plurality of stoppers 12 simultaneously from the respective containers 10. Gripper devices 44 or bar grippers 48 can be used on the stopper removal devices 26. They can also be positioned in such a way that after filling of the containers 10 has been done, the removed stoppers 12 are plated back on the containers 10 in the closing station 32. Thanks to this multifunctionality of the gripper devices, the overall construction of the system can be simplified still further.

Methods and apparatuses for sterile handling of containers are suitable particularly for filling machines involving liquid or pourable bulk goods that are subject to special sterility requirements. This is particularly the case in the pharmaceutical industry or in the case of foods. However, the use of methods and apparatuses for sterile handling of containers is not limited to those fields of use.

Claims

1-11. (canceled)

12. A method for sterile or aseptic handling of containers, including at least the following step:

before filling at least one container, checking whether the container is safely closed with a stopper by ascertaining whether an expected underpressure, preferably a vacuum, is present in an interior of the container.

13. The method as defined by claim 12, wherein the step of checking by ascertaining of the expected underpressure is effected on a basis of a force measurement of the force that is necessary for removing the stopper from the container.

14. The method as defined by claim 12, wherein the step of checking by ascertaining of the expected underpressure is effected optically.

15. The method as defined by claim 12, wherein after the step of checking whether the container is safely closed with stopper, the stopper is removed; the container is filled; and the container is then closed with the removed stopper or another stopper.

16. The method as defined by claim 13, wherein after the step of checking whether the container is safely closed with stopper, the stopper is removed; the container is filled; and the container is then closed with the removed stopper or another stopper.

17. The method as defined by claim 14, wherein after the step of checking whether the container is safely closed with stopper, the stopper is removed; the container is filled; and the container is then closed with the removed stopper or another stopper.

18. The method as defined by claim 15, wherein before the step of checking whether the container is safely closed with a stopper is done, the container is closed by the stopper, with a generation of an underpressure, preferably a vacuum, in an interior of the container.

19. The method as defined by claim 16, wherein before the step of checking whether the container is safely closed with a stopper is done, the container is closed by the stopper, with a generation of an underpressure, preferably a vacuum, in an interior of the container.

20. The method as defined by claim 17, wherein before the step of checking whether the container is safely closed with a stopper is done, the container is closed by the stopper, with a generation of an underpressure, preferably a vacuum, in an interior of the container.

21. The method as defined by claim 18, wherein after the container is closed by the stopper and the generation of an underpressure or a vacuum in the interior of the container, the closed container is sterilized.

22. The method as defined by claim 19, wherein after the container is closed by the stopper and the generation of an underpressure or a vacuum in the interior of the container, the closed container is sterilized.

23. The method as defined by claim 20, wherein after the container is closed by the stopper and the generation of an underpressure or a vacuum in the interior of the container, the closed container is sterilized.

24. The method as defined by claim 12, wherein the step of checking whether the container is safely closed with a stopper is done under clean room conditions.

25. The method as defined by claim 23, wherein the step of checking whether the container is safely closed with a stopper is done under clean room conditions.

26. An apparatus for sterile or aseptic handling of containers, including a testing unit for checking a container as to whether it is safely closed with a stopper, the testing unit ascertaining whether an expected underpressure, preferably a vacuum, is present in an interior of the container.

27. The apparatus as defined by claim 26, wherein the testing unit includes an optical signal transducer with a receiver which together check whether an expected underpressure, preferably a vacuum, is present in the interior of the container.

28. The apparatus as defined by claim 26, wherein the testing unit includes a force-measuring device, which ascertains the force which is necessary for removing the stopper from the container, in order to ascertain whether an expected underpressure, preferably a vacuum, is present in the interior of the container.

29. The apparatus as defined by claim 26, wherein a gripper device is provided, which before the containers are filled, removes the stopper and sets the stopper back onto the container after the container is filled.

30. The apparatus as defined by claim 27, wherein a gripper device is provided, which before the containers are filled, removes the stopper and sets the stopper back onto the container after the container is filled.

31. The apparatus as defined by claim 28, wherein a gripper device is provided, which before the containers are filled, removes the stopper and sets the stopper back onto the container after the container is filled.