BETA COMPONENT OF A TRANSFER SYSTEM FOR A STERILE ISOLATION AREA, STERILE ISOLATION AREA, ASEPTIC FILLING SYSTEM AND A METHOD FOR OPERATING SUCH A FILLING SYSTEM

Description

[0001] The present invention relates to a beta component of a transfer system for a sterile isolation area, a sterile isolation area, an aseptic filling system and a method for operating such a filling system.

[0002] The filling system is used to fill a flowable medium, also referred to as a product, into sealable containers. The filling process takes place under sterile, germ- and contamination-free conditions.

[0003] Such aseptic filling systems are typically designed with an isolation zone, also known as an isolator, that is closed to the outside. The isolation zone, or isolator, forms a closed environment with an atmosphere that meets specific requirements for purity and freedom from contamination.

[0004] The isolation area is separated from the operating area by a partition or isolator wall. Operating personnel may be present in the operating area; a sterile environment is not available here.

[0005] In a filling system, a filling device is arranged in the isolation area. This device is designed to fill the medium or product into sealable containers using a filling needle. The filling device is also referred to as the filling path.

[0006] The partition typically includes an alpha port of a transfer system, which, together with the beta component, forms a type of lock designed to introduce objects from the operating area into the isolation area, while maintaining sterility in the isolator / isolation area.

[0007] Until now, the filling device or the filling path for aseptic filling in the isolation area or isolator has been set up by the operating personnel using gloves, i.e. the operating personnel mounts the filling needle in the filling needle holder of the filling device and then connects the lines connected to the filling needle via pumps to the product bag in which the medium or product to be filled is held.

[0008] In addition to a filling needle, it may also be necessary to insert other items.

[0009] Prefabricated and pre-sterilized filling paths are also known. However, here too, the filling path must be installed by the operating personnel using gloves. There are also systems in which the filling path is installed in the isolator before the biodecontamination cycle with hydrogen peroxide (H2O2) and in which, after decontamination, the filling needle is removed automatically, e.g., with the help of a robot, from a quiver located in the isolator. The quiver is attached over the filling needle and is intended to prevent hydrogen peroxide from penetrating the filling needle and thus the filling hose. The disadvantage of this solution, which is known from practice, is that the filling path can be contaminated by H2O2, since the filling path is already in the isolator during the biodecontamination cycle.

[0010] US 4 534 389 A and US 2017 / 137765 A1 each disclose a transfer system having features of claim 1.

[0011] EP 2 735 317 A1 describes a beta component of a transfer system according to the preamble of claim 1.

[0012] The present invention is based on the object of providing an advantageous method for introducing objects through a transfer system. In particular, the filling needle required in the isolation area should be able to be introduced safely and without contamination.

[0013] The object is achieved by a beta component according to claim 1, by a sterile isolation area according to claim 2, a filling system according to claim 3 and a method according to claim 10.

[0014] Transfer systems are used for contamination-free material transfer into and out of isolators. They are considered the safest method for bidirectional transfer in aseptic or toxic work areas without containment or breach of sterility.

[0015] Transfer systems consist of two main components, an alpha port and a beta component, which, when docked, form a double-door system.

[0016] The Alpha Port comprises an Alpha flange and an Alpha locking unit. The Alpha flange is permanently integrated into the partition wall of the isolation area (the isolator wall). The Alpha locking unit is pivotably mounted on the Alpha flange (similar to a door).

[0017] The Alpha flange is often made of stainless steel. The Alpha closure unit is often made of plastic. The Alpha port is usually equipped with a mechanical safety mechanism that prevents the Alpha closure unit from opening in the absence of a Beta component.

[0018] The second main component is the aforementioned beta component. The beta component includes a receiving chamber, a beta flange, a casing that defines the receiving chamber, and a beta locking unit. The beta locking unit is removably attached (like a lid) to the beta flange for opening and closing the receiving chamber. The beta locking unit essentially forms a lid that can be removed from the receiving chamber.

[0019] The Beta flange and the Beta locking unit are designed to couple with the Alpha flange and the Alpha locking unit of the Alpha port of the transfer system.

[0020] During coupling, the Beta flange and Alpha flange, as well as the Beta locking unit and Alpha locking unit, are connected. When coupled, the Beta locking unit and Alpha locking unit form a locking unit and can only be opened and closed together.

[0021] Once the alpha and beta components are connected, they form a sealed unit. The seal is ensured, for example, by lip seals on the newly created unit, which can be opened without disrupting the sterile containment. Once the alpha and beta components are connected, for example, by bayonet locks, the locking mechanism is released, and the closure unit (coupled beta closure unit and alpha closure unit) can be opened inside the isolator.

[0022] According to the invention, the beta component comprises a holding device for holding an object, in particular a filling needle, in a defined position and orientation. The holding device is arranged on a side of the beta closure unit facing the receiving space, in particular, wherein a filling needle is held by the holding device.

[0023] This allows an object held in the holder to be moved into the isolation zone by pivoting the locking unit (coupled beta locking unit and alpha locking unit). For example, the locking unit can be opened automatically from the inside, i.e., from the isolation zone.

[0024] According to the invention, a sterile isolation area is also provided with a partition wall separating it from a non-sterile operating area, wherein the partition wall comprises an alpha port of a transfer system for introducing objects from the operating area into the isolation area. In particular, a filling device is arranged in the isolation area, which is designed to fill a medium into sealable containers by means of a filling needle. According to the invention, a beta component with the holding device described above is coupled to the alpha port. When the closure unit, which is formed by the coupled alpha closure unit and beta closure unit, is opened, the holding device is moved into the interior of the isolation area. Accordingly, it is not necessary to intervene in the receiving space of the beta component to remove the held object.When the locking unit (formed by a coupled alpha locking unit and a beta locking unit) is opened, it is pivoted into the isolation area. Since the holding device is arranged on the beta locking unit, it also pivots into the isolation area and the held object is accessible without spatial restrictions and can be removed there.

[0025] According to the invention, a filling system with a sterile isolation area, as just described, is also provided, wherein a handling device is arranged in the isolation area, which is designed to open the beta closure unit and the alpha closure unit in the coupled state (i.e., as described above, to open the closure unit formed by the coupled beta closure unit and alpha closure unit). Alternatively or additionally, the handling device can also be designed to remove the object held in the holding device, in particular the filling needle, from the holding device and / or to place it in the holding device.

[0026] The opening of the locking unit (coupled beta locking unit and alpha locking unit) can be automated via an automated opening mechanism that is separate from the handling device and can be operated from the operating area.

[0027] The filling system according to the invention allows a biodecontamination cycle to be carried out in a closed isolation area. This creates a germ- and contamination-free environment in the isolation area. For example, after the biodecontamination cycle, the beta component is docked to the alpha port of the transfer system. The closure unit (coupled beta closure unit and alpha closure unit) is then opened, for example, by the handling device, such as the robot arm. The closure unit can also be opened automatically from the outside (e.g., via a manually operated mechanism or with the aid of a motor).

[0028] The filling system can comprise a detection unit configured for machine vision, whose field of view includes at least the transfer system, so that the position of the filling needle can be detected by the detection unit. This simplifies the handling device's automated handling of the filling needle. The movement path of the handling device can be flexibly adjusted depending on the position of the filling needle.

[0029] It can be provided that the beta closure unit (or the entire closure unit formed by the coupled beta closure unit and alpha closure unit) can be transferred into a fixed open position upon opening, in which its position is defined. This can be achieved, for example, via a stop or a locking device. The beta closure unit and thus the holding device attached to it are located in a predetermined position when opened. This simplifies the removal of the object held in the handling device.

[0030] The following explanations refer to the beta component, the sterile isolation area, and the filling system. The beta component can comprise a casing for the receiving space that can be removed from the beta flange. The casing can be formed, for example, by a flexible plastic bag or a dimensionally stable, sterilizable container. The casing can also be designed as a semi-dimensionally stable bellows unit. A casing designed in this way can be compressible toward the beta flange or variable in its extension, but rigid transversely to it.

[0031] The filling needle is typically connected to a hose that extends out of the receiving chamber. At the end facing away from the filling needle, this hose typically has a sterile connector for connecting to a storage container. The hose (also referred to as the filling hose) can be manually guided back into the receiving chamber during dismantling, but it is also possible for the Beta component to include a retrieval device for the filling hose, which moves the filling hose back into the receiving chamber during dismantling, i.e. when the filling needle is moved back into the receiving chamber. For example, a spring element can be provided for this purpose. This can be arranged around the filling hose and retracts it into the receiving chamber during dismantling. This can prevent the filling hose from becoming crushed when the Beta closure unit is closed.

[0032] The hose section located in the receiving space is typically longer than the distance of the transfer system from the filling needle position provided in the insulator. If the sheath is designed to be flexible, e.g., as a plastic bag, the bag itself can be longer than the distance of the transfer system from the filling needle position provided in the insulator. When the filling needle is moved, the bag (sheath) can be moved toward the transfer system, compressed, or folded.

[0033] When shutting down the filling system or when a filling process is interrupted, the filling needle can be returned from the handling device to the holding device. The hose can be returned to the bag, for example, by pulling on the compressed bag (beta bag or beta bag), allowing the beta closure unit to be closed without crushing the hose. This pulling operation can be performed by the operating personnel outside the isolator without having to intervene in the isolator.

[0034] Advantages of the invention and its various developments include the avoidance of errors through the possibility of automated setup and increased product safety by eliminating the need for glove interventions. Furthermore, time can be saved when setting up the filling path. By using single-use components, the entire filling path, i.e. filling needle and hose, including the single-use bag (beta bag) can be disposed of after production. This is particularly advantageous when filling toxic products. The filling path can be upgraded after the biodecontamination cycle and is not exposed to H2O2. In other words, the filling needle and hose are located outside the isolation area during the decontamination cycle.

[0035] As mentioned above, the object is also achieved by a method for operating a filling plant as described in this application.

[0036] The method comprises the following steps: Attaching the beta component to the alpha port in the partition. During this attachment, the filling needle is positioned in the receiving space of the beta component in the holder device.

[0037] Conduct a decontamination cycle in the isolation area, particularly using H2O2. This step can be performed before, but especially after, the beta component is applied.

[0038] Opening the closure unit (i.e., the entire closure unit formed by the coupled Beta closure unit and Alpha closure unit), particularly by means of the handling device. However, opening is also possible using an opening mechanism integrated, for example, into the Alpha flange.

[0039] Removing the filling needle from the holding device, in particular by means of the handling device.

[0040] Placing the filling needle in a needle holding device of the filling device, in particular by means of the handling device.

[0041] In particular, removing the filling needle from the needle holding device of the filling device, in particular by means of the handling device; in particular, placing the filling needle in the receiving space, in particular by means of the handling device, in particular in the holding device.

[0042] The invention is described in more detail below with reference to the figures, wherein identical or functionally identical elements may be provided with reference numerals only once. Figure 1 an aseptic filling system; Figure 2 the aseptic filling system from Figure 1 in an operational state; Figure 3 a transfer system (Alpha port with docked Beta component); and Figure 4 the transfer system from Figure 3 in an open state.

[0043] Figure 1shows an aseptic filling system 10. The filling system 10 is used to fill a medium 32 into sealable containers 34. The aseptic filling system 10 is designed with an outwardly closed isolation area 12, which is separated from an operating area 14 by a partition wall 16.

[0044] A filling device 18 is arranged in the isolation area 12. A handling device 40 is also arranged in the isolation area 12, which will be discussed in more detail later.

[0045] The filling device 18 comprises a needle holding device 19, which is designed to hold a filling needle 20 or in which the filling needle 20 can be arranged to perform filling processes. The needle holding device 19 forms a holder for the filling needle 20. The needle holding device 19 can also be arranged in the filling device 18 in such a way that it is moved by the latter during the filling processes.

[0046] The partition wall 16, by which the isolation area 12 is separated from the operating area 14, comprises a transfer system 22. The transfer system 22 serves for the introduction, in particular the aseptic transfer, of objects from the operating area 14 into the isolation area 12.

[0047] The transfer system 22 comprises a replaceable beta component 24 and an alpha port 27 fixedly arranged in the partition wall 16.

[0048] The replaceable Beta component 24 is formed with a Beta flange 26 (in Fig. 1 shown partially transparent). The replaceable beta component 24 further comprises a removable or openable beta closure unit 30 (see, for example, Figure 2 ). The Beta closure unit 30 is designed like a lid.

[0049] The Alpha port 27, which is fixedly arranged in the partition wall 16, comprises an Alpha flange 28 connected to the partition wall 16 and an Alpha closure unit 29 which is pivotally mounted relative to the Alpha flange 28.

[0050] The beta component 24 is designed for coupling to the alpha port 27, which is fixedly arranged in the partition wall 16. For coupling, the beta flange 26 is sealingly connected to the alpha flange 28. The beta closure unit 30 is connected to the alpha closure unit 29, so that both are sealingly in contact with each other with their respective outer sides and can only be moved together. In the connected state, the beta closure unit 30 and the alpha closure unit 29 form a closure unit 31 of the transfer system 22. In the closed state, the alpha closure unit 29 forms the side of the closure unit 31 facing the insulation area 12, and the beta closure unit 30 forms the side of the closure unit 31 facing away from the insulation area 12. The closure unit 31 pivots into the insulation area 12 when opened.

[0051] To couple the Alpha port 27 and the Beta component 24, they are connected to each other by means of a bayonet lock through a rotational movement of the Beta component 24. The Beta flange 26 engages sealingly with the Alpha flange 28. Accordingly, the Beta closure unit 30 engages sealingly with the Alpha closure unit 29. Other coupling types are also within the scope of the invention.

[0052] The beta component 24 comprises a receiving space 36 accessible via the beta closure unit 30 and otherwise closed, and a casing 44 of the receiving space 36 that can be removed from the beta flange 26. The casing 44 is formed in this case by a flexible plastic bag (also referred to as a beta bag). The casing 44 can also be formed by a dimensionally stable, sterilizable container, e.g., a stainless steel container.

[0053] The beta closure unit 30, as part of the closure unit 31, opens or closes the receiving space 36 toward the insulation area 12 when assembled. The beta closure unit 30 is designed as a rounded, lid-like unit for this purpose. The alpha closure unit 29 is pivotally mounted on the alpha flange 28 via a hinge mechanism 45. The beta closure unit 30 is removable from the beta flange 26 so that, when coupled to the alpha closure unit 29, it follows its pivoting movement upon opening. Fig.4 It is clearly visible that the transfer system 22 includes a locking mechanism 60. The locking mechanism 60 can only be unlocked when the alpha locking unit 29 is coupled to the beta locking unit 30.

[0054] To insert the filling needle 20 into the insulation area 12, it is first arranged in the beta component 24 in the receiving space 36. The filling needle 20 is connected to a hose 43 that extends out of the receiving space 36 and, at its end facing away from the filling needle 20, includes a sterile connector 48 for connection to a storage container 46.

[0055] In the receiving space 36 of the beta component 24, a holding device 50 is arranged for the precise positioning of the filling needle 20. The holding device 50 is, as shown in Figure 3 and 4 clearly shown, arranged on the removable beta closure unit 30. If the beta component 24 is coupled to the alpha port 27 and the closure unit 31 is opened, the filling needle 20 held in the holder device 50 is moved into the isolation area 12.

[0056] The handling device 40 arranged in the isolation area 12 is designed as a robot arm in the present case. The handling device 40 is designed to open the closure unit 31 (alpha closure unit 29 and beta closure unit 30 connected to each other in the coupled state) and to remove the filling needle 20 from the holder device 50 and insert it into the needle holding device 19. After use of the filling needle 20, the filling needle 20 can be moved back into the holder device 50 by means of the handling device 40.

[0057] The filling system 10 comprises an optional detection unit 42 which is configured for machine vision and whose field of view comprises the transfer system 22 and, in the present case, the needle holding device 19, so that a position of the filling needle 20 can be detected by the detection unit 42 and the handling device 40 can be controlled or regulated accordingly in order to remove the filling needle 20 from the holding device 50 and to place it in the needle holding device 19 and, after use, to transfer it back into the holding device 50.

[0058] When removing the filling needle 20, the flexible bag-like sheath 44 is Figure 2 shown compressed, so to speak, since the hose 43 is pulled into the insulation area.

[0059] The casing 44 can also be designed as a semi-rigid bellows unit. A casing 44 designed in this way can be compressible in the direction of the beta flange 26 or variable in its extension, but rigid transversely thereto.

[0060] The locking unit 31 (or the alpha locking unit 29 and the beta locking unit 30 coupled to it) can be transferred into a fixed open position when opened, as shown in Figure 2 is shown. In the fixed open position, the alpha locking unit 29 or the entire locking unit 31 and thus also the beta locking unit 30 and the holding device 50 arranged on it are fixed in their position.

[0061] The filling needle 20 is connected via the hose 43 to the storage container 46 containing the medium 32 by means of the sterile connector 48. The storage container 46, in turn, is connected via a container-side sterile connector 52 to a hose section that passes through a peristaltic pump 56. A medium filter 58 is arranged in the connecting hose line between the peristaltic pump 56 and the sterile connector 48 on the filling needle 20 side.

Claims

1. Beta-component (24) of a transfer system (22) comprising a receiving space (36), a beta-flange (26), a casing (44) defining the receiving space (36), and a beta-closure unit (30), the beta-closure unit (30) being detachably attached to the beta-flange (26) for opening and closing the receiving space (36), and the beta-flange (26) and the beta-closure unit (30) being designed for coupling to an alpha-flange (28) and an alpha-closure unit (29) of an alpha-port (27) of the transfer system (22), characterized in that the beta-component (24) has a holding device (50) for holding an object (20), in particular a filling needle (20), in a defined position and orientation, characterized in that the holding device (50) is arranged on a side of the beta-closure unit (30) facing the receiving space (36), in particular a filling needle (20) being held by the holding device (50).

2. Sterile isolation region (12) having a partition (16) by which it is separated from a non-sterile operating region (14), the partition (16) comprising an alpha-port (27) of a transfer system (22) for introducing objects (24) from the operating region (14) into the isolation region (12), in particular a filling device (18) being arranged in the isolation region (12), which filling device is designed to fill a medium (32) into closable containers (34) by means of a filling needle (20), characterized in that a beta-component (24) according to claim 1 is coupled to the alpha-port (27), the holding device (50) being moved into the interior of the isolation region (12) upon opening of a closure unit (31) of the transfer system (22), which is formed by the alpha-closure unit (29) and beta-closure unit (30) coupled to each other.

3. Filling system (10) comprising a sterile isolation region (12) according to claim 2, wherein a handling device (40) is arranged in the isolation region (12), which handling device is designed to open the beta-closure unit (30) and the alpha-closure unit (29) in the coupled state and / or to remove the object held in the holding device (50), in particular the filling needle (20), from the holding device (50) and / or to place it therein.

4. Filling system (10) according to claim 3, characterized in that it comprises a detection unit (42) which is set up for machine vision and the field of view of which comprises at least the transfer system (22), so that a position and / or orientation of the object, in particular of the filling needle (20), can be detected by the detection unit (42).

5. Sterile isolation region (12) or filling system (10) according to claim 2, characterized in that the closure unit (31), which is formed by the alpha-closure unit (29) and beta-closure unit (30) coupled to each other, can be transferred into a fixed open position during opening, in which its position is determined.

6. Beta-component (24), sterile isolation region (12) or filling system (10) according to any of the preceding claims, characterized in that the casing (44) of the receiving space (36) of the beta-component (24) is designed to be detachable from the beta-flange (26), in particular the casing (44) being formed by a flexible plastic bag or being formed by a dimensionally stable, sterilizable container.

7. Beta-component (24), sterile isolation region (12) or filling system (10) according to any of the preceding claims, characterized in that the filling needle (20) is connected to a tube (43) which extends out of the receiving space (36) and in particular comprises, at its end facing away from the filling needle (20), a sterile-connector (48) for connection to a feed tank (46).

8. Beta-component (24), sterile isolation region (12) or filling system (10) according to the previous claim, characterized in that the beta-component (24) comprises a return device for the tube (43), which, during teardown, i.e. when the filling needle (20) is moved back into the receiving space (36), also moves the tube (43) back into the receiving space.

9. Beta-component (24), sterile isolation region (12) or filling system (10) according to any of the preceding claims, characterized in that the beta-flange of the beta-component (24) and the alpha-flange (28) of the alpha-port (22) are designed to be connected to each other with a bayonet lock and the beta-closure unit (30) and the alpha-closure unit (29) are designed to be connected to each other with a bayonet lock.

10. Method for operating a filling system (10) according to any of the preceding claims 3 to 9, the method comprising the steps of: attaching the beta-component (24) to the alpha-port (27) in the partition (16), the filling needle (20) being arranged in the receiving space (36) of the beta-component (24) in the holding device (50); performing a decontamination cycle in the isolation region (12); characterized in that the method comprises the following steps: opening the transfer system (22) by means of the handling device (40); removing the filling needle (20) from the holding device (50) by means of the handling device (40); placing the filling needle (20) in a needle holding device (19) of the filling device (18) by means of the handling device (40); in particular, removing the filling needle (20) from the needle holding device (19) of the filling device (18) by means of the handling device (40); in particular, placing the filling needle (20) in the receiving space (36) by means of the handling device (40), in particular in the holding device (50).