EP2190747B1 - Method and device for the sterile or aseptic handling of containers - Google Patents

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

The invention is based on a method and a device for the sterile or aseptic handling of containers according to the preamble of the independent claims. From the EP 1447 328 B1 A method for the sterile dosage of vials is already known. After assembling the vial and cap, they are rinsed. Then a protector is put on. In an autoclave, the assembly is sterilized. After cooling and removal of protector and cap, the liquid is filled into the vial. Subsequently, the vial is closed again. Filling is recorded with a video camera for documentation purposes. After encapsulation, the vial is provided with an identification of the dosing time by means of a laser beam.

It is an object of the present invention to reduce the handling steps, in particular in the run-up to the filling process. This object is solved by the features of the independent claims.

Inventive method and apparatus for sterile handling of containers are characterized in that it is checked whether a container is sealed intact with a stopper by determining whether in the interior of the container an expected negative pressure, preferably vacuum, is still present. Thus, the combination of the with the stopper be sterilized sealed container and also be supplied in this combination for filling. This prevents that a separate feeding of the plug must be made to close with the necessary sterilization processes. Furthermore, the integrity check ensures that the supplied containers with stoppers comply with the sterility requirements, since they are properly sealed containers, the interior of which in each case still meets the sterility requirements. This concept also makes it possible to use the stopper to be removed during the filling operation, preferably with the same handling device, after closing to close it. On a device for separate Stopfenzuführung can be dispensed with. The already-to-be-provided manipulator, for example a gripping device, for stopper removal is preferably also used for closing the filled container. As a result, the cost of the system can be reduced again.

In an expedient development, it is provided that the checking of the expected negative pressure takes place on the basis of a force measurement of that force which is necessary for the removal of the plug from the container. A corresponding force measuring device can be provided at the plug removal device, for example a manipulator, or is present anyway. The force is a measure of whether the interior of the container is still subjected to the expected negative pressure, which suggests the integrity of the arrangement container plug. If the vacuum is still present, the force which is required to remove the plug is significantly greater than would be the case in the case of a damaged container-plug connection with concomitant internal pressure compensation. Thus, the force is a good indicator of the integrity of the stoppered container assembly. Since the manipulator for removing the plug anyway has to come into mechanical contact with this, also a force measurement is easy to implement.

In an expedient development, it is provided that the checking of the expected negative pressure takes place optically. For this purpose, the container is preferably irradiated with a laser beam. On the basis of the optical spectrum of the incoming radiation on the other side can draw conclusions about the medium or to be drawn to the pressure conditions inside the container. At negative pressure is to be expected with a changed spectrum, as this would be the case at ambient pressure, thus in the situation of a no longer properly sitting plug. Such optical inspection devices can be installed without much additional effort and are known in principle.

In an expedient development it is provided that a plurality of sealed containers are placed in at least one tray. The containers located in the tray, closed with plugs and applied in the interior negative pressure, are subsequently sterilized. The sterilization can be done, for example, the manufacturer of the containers and plugs. However, it would also be conceivable to do so immediately before bottling. Handling by means of trays simplifies transport and feeding of the containers to downstream process steps.

In an expedient refinement, it is provided that checking whether a container is closed intact with a stopper takes place under clean-room conditions. This can be ensured that when removing the plug for checking or for subsequent filling of the container a re-sterilization of the container no longer needs to be done. This reduces the necessary steps to sterilize the containers.

Further expedient developments emerge from further dependent claims and from the description.

An embodiment of the method and apparatus for sterile handling of containers is dargstellt in the figures and will be described in more detail below.

• Die Figur 1 schematisch die drei Prozessschritte vom Verschließen der Behältnisse bis hin zum Sterilisieren,
• die Figur 2 die Prozessschritte vom Überprüfen, ob das Behältnis unversehrt mit einem Stopfen verschlossen ist, bis hin zum Verschließen der befüllten Behältnisse,
• die Figur 3 das Überprüfen des Unterdrucks mittels optischer Verfahren,
• die Figur 4 das Überprüfen des Unterdrucks mittels mechanischer Kraftmessung, sowie
• die Figur 5 einen Balkengreifer zum Entnehmen bzw. Aufsetzen mehrerer Stopfen.

Show it:

• The FIG. 1 schematically the three process steps from closing the Containers right through to sterilization,
• the FIG. 2 the process steps from checking that the container is closed intact with a stopper, to closing the filled containers,
• the FIG. 3 checking the negative pressure using optical methods,
• the FIG. 4 Checking the negative pressure by means of mechanical force measurement, as well
• the FIG. 5 a beam gripper for removing or placing a plurality of plugs.

In a vacuum chamber 14, a plug 12 is placed by a plug closure 16 on a container 10 and closed by applying a negative pressure. This creates a negative pressure in the interior of the container 10. The containers 10 sealed in this way under reduced pressure, preferably a vacuum, are then filled by trays 19 into trays 18, so that a plurality of containers 10 closed with stoppers 12 are now positioned in a tray 18. This tray 18 with the containers 10 disposed therein enters a sterilizer 20, in which the containers 10 are sterilized. Subsequently, the trays 18 are provided with an outer packaging as transport protection.

The thus sterilized containers 10 are then placed in a clean room 22 in which several stations are arranged. One of them is a test unit 24. This unit 24 checks whether there is the expected negative pressure in the interior of the still closed container 10, as an indicator of an intact, with the stopper 12 still properly closed container 10. As part of a stopper removal device 26 removes a corresponding manipulator or a gripping device 44 the plug 12. Subsequently, the opened container 10 - if it has been recognized as properly closed - filled in a filling machine 28. Optionally, filled containers 10 may be subjected to an internal process control 30, which determines whether the container 10 has been filled with the correct amount of liquid. In a closing station 32, which may also be part of the filling machine 28, the filled container 10 is closed again with the stopper 12.

According to FIG. 3 Verification of whether the container is sealed intact with a stopper is carried out. For this purpose, a laser 36 irradiates 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 about whether the interior of the container 10 still prevails an expected negative pressure. This can be seen whether the container 10 is still intact with the stopper 12 is closed.

In an alternative embodiment of the test unit 24, a gripping device 44 is now provided with a gripper 42, which serves to remove the plug 12 from the container 10. The gripping device 44 is also provided with a force measuring device 46, which determines a measure of the force required to remove the plug 12. On the basis of the detected force is detected, whether in the interior of the container 10 nor the expected negative pressure prevails or whether the container 10 is not properly closed. Upon application of a negative pressure or vacuum inside the container 10, a significantly higher force for removing the plug 12 is required, thus providing information about the integrity of Veschlusses of the container 10 with the stopper 12. The container 10 is on its underside with a Flange 40 is provided, which cooperates with a holding device, not shown, for applying a counter force for removing the plug 12.

According to FIG. 5 the top view of a beam gripper 48 is shown with a plurality of openings for receiving a plurality of plugs 12th

The devices shown in the figures operate as follows. The containers 10 are preferably filled in the pharmaceutical sector with drugs under aseptic conditions and closed again with the stopper 12. The containers 10 may be, for example, vials or bottles made of glass or plastic or the like. The liquid pharmaceuticals filled in the containers 10 are removed in the hospital or at the doctor, for example, by puncturing the stopper 12 with an injection needle. The plug 12 is equipped accordingly.

In order to reduce the sterilization steps prior to 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 example by the manufacturer of the containers 10 and / or the plug 12. In order to reliably recognize in the subsequent sterilization step that the container 10 is still properly closed by the stopper 12 or the closure is intact prior to further processing, a negative pressure, preferably a vacuum, is created in the interior of the container 10. This is done in the vacuum chamber 14, in which the container 10 is closed by means of plug closure 16 with the stopper 12. The plug closure device 16 can be, for example, a manipulator, that is to say a robot with a gripper. Under certain circumstances, it could also be provided to arrange a protector via the stopper 12, which protects the stopper 12 for the further handling operations. However, this protector is not mandatory.

In a further step, the respective sealed containers 10 are fed by the gripping device 19 to a tray 18. The tray 18 has receptacles and openings which are matched to the outer diameter of the container 10, so that a plurality of these containers 10 are received in the tray 18 and thus can be simultaneously supplied to the further processing operations. Although this so-called pre-formatting is helpful for further handling, it is not absolutely necessary.

The thus loaded with containers 10 tray 18 is now fed to a sterilizer 20. The negative pressure or the vacuum remains in the interior of the containers 10 continue to exist, unless the closures have remained intact, that is, the plug 12 closes the container 10 in the correct manner, so that the negative pressure can not escape. The sterilizer 20 relies on conventional sterilization methods, which are based for example on radiation sterilization (for example by means of gamma rays), heat generation, for example by means of plasma, or electron beams or the like. The sterilizer 20 could either be inline, that is as part of the filling process and thus in the spatial vicinity of the filling machine 28, take place. Just as well, however, the sterilizer 20 could be arranged spatially separated from the filling machine 28, for example, in special companies that perform the sterilization of container 10 with attached plug 12 with fitting in the interior of the container 10 negative pressure. By the sterilization process and the interior of the container 10 is sterilized. At a sterilizer 20 spatially remote from the filling machine 28, the tray 18 could be correspondingly packaged to be transported to the filling machine 28 under sterile conditions.

After sterilization, the sealed containers 10 enter the clean room 22. Previously, any packaging that may be present is removed from the containers 10 or the trays 18. Also arranged in the tray 18 containers 10 could be separated again. Alternatively, the containers 10 can still be arranged on the tray 18 are supplied to the clean room 22.

In the clean room 22 is the test unit 24. However, it could also be arranged in a separate clean room, which is separate from that of the filling machine 28. The test unit 24 determines whether the plug 12 still properly closes the container 10. This is determined on the basis of indicators of the pressure conditions in the interior of the container 10. Closes the plug 12, the container 10 still properly, so prevails in the interior nor a negative pressure or a vacuum. In case of failure, however, the interior will be exposed to ambient pressure. Different embodiments of the test unit 24 will be later in connection with the FIGS. 3 and 4 explained in more detail. Containers 10, in which there is no expected negative pressure in the interior, are removed and not filled because they do not meet the sterility requirements.

In integral containers 10 - in the interior there was still the expected negative pressure - the respective plugs 12 are removed. This can be done, for example, by means of the gripping device 44 also arranged in the clean room 22. The opened container 10 is now in the filling machine 28 with the desired liquid in the desired amount dosed. In the context of an in-process control 30, the desired filling quantity is checked and, if necessary, corrective measures are initiated during deviations. For this purpose, for example, the weight or the level of the filled container 10 is determined, for example by means of X-radiation or optically.

Subsequently, in the closing station 32, the corresponding stopper 12 is again placed on the filled container 10. For this purpose, preferably the same gripping device 44 could hold the removed plug 12 during the filling process and then put it back on in the course of the closing. A separate stopper feed would be eliminated. The gripping device 44 could be a so-called pick and place device. Optionally, a further freeze-drying may be necessary before closing with the stopper 12 in order to remove condensate from the container 10.

Subsequently, the sealed container 10 is further transported to a capping station, not shown, which still touches a cap on the container 10 closed with the stopper 12 and connects to the container 10, for example by means of crimping. A corresponding marking of the container 10 with regard to production information or the like, for example by means of a laser, can still follow.

The test unit 24 can fall back on any physical principles that are suitable to carry out a vacuum detection or vacuum detection in the interior of the container 10. For this purpose, for example, optical methods are suitable when a laser 36 irradiates the interior of the container 10. The incident radiation is detected by a receiver 38. On the basis of the frequency spectrum can be detected, for example, whether in the interior of the container 10 is applied a vacuum or not. So the optical Absorbtionsverhalten in vacuum is different than at ambient pressure. It would also be possible to arrange the receiver 38 on the same side as the laser 36 and to redirect the radiation passing through the interior through a reflector to the receiver 38.

A further advantageous embodiment of the test unit 24 is in FIG. 4 shown. To fill the container 10, the plug 12 must be removed anyway. This is done by the gripping device 44. This gripping device 44 can now be additionally equipped by a force measuring device 46 or this is anyway present in a robot arm. Based on the force required to remove the plug 12 from the container 10, conclusions can be drawn on the prevailing in the interior of the container 10 pressure conditions. Thus, a significantly increased force is required to remove the plug 12 at vacuum or vacuum from the container 10 than at ambient pressure. The detected force is compared with a threshold. If the force is below the limit, then this is an indication of a no longer intact container 10, as based on the detected force, everything points to a broken vacuum.

In order to facilitate the removal of the plug 12, the container 10 is provided at the bottom with a surrounding this annular mounting flange 40. The upper side of the fastening flange 40 is surrounded by a stationary holding device 50, so that the container 10 can not be moved upward during the removal of the plug 12. The gripping device 44 can also be designed as a bar gripper 48. Then it becomes possible for a plurality of plugs 12 to be simultaneously removed from the respective container 10. Gripping devices 44 or beam grippers 48 can be used on the plug removal devices 26. Furthermore, they can be positioned so that the removed plugs 12 are placed back on the containers 10 after the filling of the containers 10 at the closing station 32. Thanks to this multiple functionality of the gripping devices, the overall structure of the system can be further simplified.

Methods and apparatus for sterile handling of containers are particularly suitable for filling liquid or free-flowing bulk materials, which are subject to special sterility requirements. This is the case in particular in the pharmaceutical industry or in foodstuffs. However, the use of methods and apparatus for sterile handling of containers is not limited to these fields of application.

Claims (11)

1. Method for the sterile or aseptic handling of containers (10), comprising at least the following step:

   checking, prior to at least one container (10) being filled, so that the container (10) is closed in an intact state by a stopper (12), in that it is determined whether an expected negative pressure, preferably vacuum, is present in the interior of the container (10).
2. Method according to Claim 1, characterized in that the step of checking the expected negative pressure takes place by way of measuring the force which is necessary for removing the stopper (12) from the container (10).
3. Method according to Claim 1, characterized in that the step of checking the expected negative pressure takes place optically.
4. Method according to one of the preceding claims, characterized in that, once it has been checked whether the container (10) is closed in an intact state by a stopper (12), the stopper (12) is removed, the container (10) is filled, and the container (10) is closed by the stopper (12) which has been removed or at some other stopper.
5. Method according to one of the preceding claims, characterized in that, prior to the step of checking whether the container (10) is closed in an intact state by a stopper (12), the container (10) is closed by the stopper (12) to generate a negative pressure, preferably a vacuum, in the interior of the container (10).
6. Method according to one of the preceding claims, characterized in that, once the container (10) has been closed by the stopper (12) and a negative pressure or vacuum has been generated in the interior of the container (10), the closed container (10) is sterilized.
7. Method according to one of the preceding claims, characterized in that, the step of checking whether the container (10) is closed in an intact state by a stopper (12) takes place under clean-room conditions.
8. Apparatus for the sterile or aseptic handling of containers, comprising a testing unit (24) for checking a container (10) as to whether it is closed in an intact state by a stopper (12), wherein the testing unit (24) determines whether an expected negative pressure, preferably a vacuum, is present in the interior of the container (10), the testing unit (24) being installed prior to the containers (10) being filled.
9. Apparatus according to the preceding claim, characterized in that the testing unit (24) comprises an optical signal transmitter (36) with a receiver (38), which checks whether an expected negative pressure, preferably a vacuum, is present in the interior of the container (10).
10. Apparatus according to Claim 8, characterized in that the testing unit (24) comprises a force-measuring device (46) which determines the force which is necessary for removing the stopper (12) from the container (10), for the purpose of determining whether an expected negative pressure, preferably a vacuum, is present in the interior of the container (10).
11. Apparatus according to one of the preceding apparatus claims, characterized by the provision of a gripping device (44) which removes the stopper (12) prior to the container (10) being filled and places the stopper on the container (10) again once the container (10) has been filled.

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