Beta component of a sterile isolator transfer system, sterile isolator, sterile filling system and method of operating such a filling system

Abstract

The present invention relates to a beta-component for a transfer system of a sterile isolator, a sterile isolator, a sterile filling system and a method of operating such a filling system.

Description

Technical Field

[0001] The present invention relates to a β-component for a transfer system for a sterile isolation zone, a sterile isolation zone, a sterile filling system, and a method of operating such a filling system. Background Technology

[0002] A filling system is used to fill flowable media (also known as products) into sealable containers. The filling process is carried out under sterile, germ-free, and contamination-free conditions.

[0003] This type of aseptic filling system is typically designed with an isolation zone, also known as an isolator, that is isolated from the outside. Therefore, the isolation zone or isolator creates a closed environment with an atmosphere that meets specific requirements for cleanliness and contamination-free conditions.

[0004] The isolation zone is separated from the operating area by a partition wall or isolator wall. Operators can work within the operating area; however, there is no sterile environment there.

[0005] In a filling system, filling devices are arranged in an isolated area and are designed to fill media or products into sealable containers using filling needles. These filling devices are also called filling paths.

[0006] The partition typically includes an α-port of the transfer system, which together with a β-component forms a type of airlock designed to introduce objects from the operating area into the isolation area, thereby maintaining sterility within the isolator / isolation zone.

[0007] To date, filling devices or filling paths for aseptic filling in isolation zones or isolators have been set up by operators via a glove port, whereby the operator mounts the filling needle in the filling needle hub of the filling device and then connects the tubing connected to the filling needle to the product bag via a pump, providing the medium or product to be filled into the product bag.

[0008] In addition to the filling needle, the insertion of other objects may also be necessary.

[0009] Pre-assembled and pre-sterilized filling paths are also known. However, in these cases, the filling path must still be installed by an operator via a glove port. Systems are also known that install the filling path in an isolator before a bio-decontamination cycle using hydrogen peroxide (H₂O₂), and automatically remove the filling needle from a syringe located in the isolator after decontamination, for example, with the assistance of a robot. The syringe is attached above the filling needle to prevent hydrogen peroxide from entering the filling needle and subsequently the filling tube. Practical experience shows that a drawback of this solution is that the filling path can be contaminated with H₂O₂ because it is already in the isolator during the bio-decontamination cycle. Summary of the Invention

[0010] The object of this invention is to provide an advantageous method for inserting objects via a delivery system. In particular, the filling needles required in the isolation zone should be able to be safely and contaminatedly inserted into said zone.

[0011] Transfer systems are used to transfer uncontaminated materials into or out of isolators. They are considered the safest method for bidirectional transfer in sterile or toxic work areas without contamination and / or compromise of sterility.

[0012] The transmission system consists of two main components, the α-port and the β-component, which form a dual-gate system when docked.

[0013] The α-port comprises an α-flange and an α-closure unit. The α-flange is securely integrated into the partition wall of the isolation zone (in the isolator wall). The α-closure unit (similar to a door) is pivotally arranged on the α-flange.

[0014] The α-flange is typically formed of stainless steel. The α-closure unit is typically formed of plastic. The α-port is usually equipped with a mechanical safety mechanism to prevent the α-closure unit from opening without the β-assembly.

[0015] The second main component is the aforementioned β-component. The β-component includes a receiving space, a β-flange, a housing defining the receiving space, and a β-closure unit. The β-closure unit is detachably attached (cap-like) to the β-flange for opening and closing the receiving space. The β-closure unit effectively forms a cap that can be removed from the receiving space.

[0016] The β-flange and β-closure unit are configured for connection to the α-port of the transmission system.

[0017] During the connection, the β-flange and α-flange, as well as the β-closing unit and α-closing unit, are connected to each other. When connected, the β-closing unit and α-closing unit form a closing unit and can only be opened and closed together.

[0018] Once the α- and β-components are joined, they form a closed unit. For example, a seal is ensured by a lip seal of the newly created unit, which can be opened without disrupting the sterile outer shell. If the α- and β-components are joined, for example by a snap-fit ​​connection, the lock is released, and the closed unit (the joined β- and α-closed units) can be opened inside the isolator.

[0019] According to the present invention, the β-assembly now provided has a holding device for holding an object, particularly a filling needle, in a defined position and orientation. The holding device is arranged on the side of the β-closure unit facing the receiving space, and in particular, the filling needle is held by the holding device.

[0020] This allows an object held in the holding device to be moved into the isolation zone via a pivoting closure unit (the connected β-closure unit and α-closure unit). For example, the closure unit can be automatically opened from the inside, i.e., from the isolation zone side.

[0021] According to the invention, the aseptic isolation zone is further provided with a partition wall separating it from the non-aseptic operating area. The partition wall includes an α-port of a transfer system for introducing objects from the operating area into the isolation zone. Specifically, a filling device is arranged in the isolation zone, designed to fill media into a sealable container using a filling needle. For the purposes of this invention, the β-assembly is coupled to the α-port by means of the aforementioned holding device. When the closure unit (formed by the coupled α-closure unit and β-closure unit) is opened, the holding device moves into the interior of the isolation zone. Therefore, it is not necessary to enter the receiving space of the β-assembly to remove the held object. When the closure unit (formed by the coupled α-closure unit and β-closure unit) is opened, the closure unit pivots into the isolation zone. Since the holding device is arranged on the β-closure unit, it pivots together with the β-closure unit into the isolation zone, and the held object can be accessed and removed there without spatial restrictions.

[0022] According to the present invention, a filling system having a sterile isolation zone as described above is also provided, wherein an actuating device is arranged in the isolation zone, the actuating device being designed to open the β-closure unit and α-closure unit in a connected state (i.e., to open the closure unit formed by the connected β-closure unit and α-closure unit as described above). Alternatively or additionally, the actuating device may also be configured to remove an object, particularly a filling needle, held in the holding device from the holding device, and / or place it in the holding device.

[0023] The opening of the closing unit (the connected β-closing unit and α-closing unit) can be automated via an automatic opening mechanism separate from the operating device and can be actuated from the operating area.

[0024] The filling system according to the invention allows for a bio-purification cycle to be performed in a closed, isolated zone. This provides a pathogen-free and contamination-free environment within the isolated zone. For example, after the bio-purification cycle, the β-component is connected to the α-port of the delivery system. Subsequently, the sealing unit (the coupled β-sealing unit and α-sealing unit) is opened, for example by an actuation device, such as a robotic arm. The sealing unit can also be opened automatically from the outside (e.g., via a manual operating mechanism or by means of a motor).

[0025] The filling system may include a detection unit configured for machine vision, and its field of view includes at least a transmission system, such that the position of the filling needle can be detected by the detection unit. Therefore, the manipulator can take over and / or clamp the filling needle in a simplified, automated manner. The movement path of the manipulator can be flexibly adapted to the position of the filling needle.

[0026] What can be provided is that the β-closing unit (or more precisely, the entire closure unit formed by the coupled β-closing unit and α-closing unit) can be moved to a fixed open position during opening, in which the position of the closure unit is determined. This can be achieved, for example, by means of a stop or brake. The β-closing unit and the retaining device thereon are accordingly in a predetermined position in the open state. This simplifies the removal of objects held in the operating device.

[0027] The following statements relate to β-components, aseptic isolation areas, and filling systems. β-components may include a housing of receiving space, which is detachable from the β-flange. For example, the housing may be formed from a flexible plastic bag or from a dimensionally stable, sterilizable container. The housing may also be formed as a semi-dimensionally stable bellows unit. This type of housing can be designed so that its extension toward the β-flange is compressible and / or variable, but rigid transversely to the β-flange.

[0028] The filling needle is typically connected to a tube extending out of the receiving space. At its end, away from the filling needle, the tube typically has a sterile connector for connection to the supply tank. This tube (also called the filling tube) can be manually returned to the receiving space during disassembly, but the β-assembly may also include a return device for the filling tube, which also moves the filling tube back into the receiving space during disassembly, i.e., when the filling needle is moved back into the receiving space. For example, an elastic element can be provided for this purpose, which can be arranged around the filling tube and pull the filling tube back into the receiving space during disassembly. This prevents the filling tube from being squeezed when the β-closure unit is closed.

[0029] The tube segment located in the receiving space is typically longer than the distance from the delivery system to the filling needle positioned in the isolator. If the housing is designed to be flexible in shape, such as a plastic bag, the bag itself can be longer than the distance from the delivery system to the filling needle positioned in the isolator. As the filling needle moves, the bag (housing) can move toward the delivery system and / or compress and / or fold.

[0030] During disassembly of the filling system or if the filling operation is interrupted, the filling needle can be returned from the operating device to the holding device. For example, by pulling the compressed bag (β-bag), the tube can be brought back into the bag, thereby closing the β-closing unit without squeezing the tube. This pulling can be performed by the operator outside the isolator without having to enter the isolator.

[0031] The advantages of this invention and its various further developments include the avoidance of errors due to the possibility of automated setup and improved product safety due to the elimination of the possibility of glove ports. Furthermore, time can be saved in setting up the filling path. By using disposable components, the entire filling path, or more precisely, the filling needles and tubing, along with the disposable bags (β-bags), can be discarded at the end of production. This is particularly advantageous when filling toxic products. The filling path can be set up after a bio-decontamination cycle and is not exposed to H2O2. In other words, during the decontamination cycle, the filling needles and tubing are outside the isolation zone.

[0032] As described above, the task is also accomplished by a method of operating the filling system as described in this application.

[0033] The method includes the following steps:

[0034] The β-component is attached to the α-port in the partition wall. During this attachment, the filling needle is positioned in the receiving space of the β-component within the holding device.

[0035] A purification cycle is performed in the isolation zone, particularly using H2O2. This step can be performed before, but especially after, the attachment of the β-component.

[0036] The closed unit (i.e., the entire closed unit formed by the connected β-closed unit and α-closed unit) can be opened, particularly by means of an actuating device. However, it is also possible, for example, to open it by means of an opening mechanism integrated in the α-flange.

[0037] Remove the filling needle from the holding device, especially by means of a manipulator.

[0038] The filling needle is placed in the needle holding device of the filling device, especially by means of a manipulator.

[0039] In particular, the filling needle is removed from the needle holding device of the filling device, especially by means of an actuating device;

[0040] In particular, the filling needle is placed in the receiving space, especially in the holding device, and especially by means of the manipulating device. Attached Figure Description

[0041] The invention is described in more detail below with reference to the accompanying drawings, wherein the same or functionally identical elements (if applicable) are marked only once by reference numerals.

[0042] Figure 1 It is an aseptic filling system;

[0043] Figure 2 It is in operation mode. Figure 1 The aseptic filling system shown;

[0044] Figure 3 It is a transmission system (with an α-port of a docking β-component); and

[0045] Figure 4 It is in the open state. Figure 3 The transmission system. Detailed Implementation

[0046] Figure 1 An aseptic filling system 10 is shown. The filling system 10 is used to fill media 32 into a sealable container 34. The aseptic filling system 10 is configured with an isolation zone 12 isolated from the outside, which is separated from the operating zone 14 by a partition wall 16.

[0047] A filling device 18 is arranged in the isolation zone 12. In the present case, the operating device 40 is also arranged in the isolation zone 12, which will be discussed in detail later.

[0048] The filling apparatus 18 includes a needle holding device 19 configured to hold a filling needle 20, and the filling needle 20 can be correspondingly arranged in the needle holding device 19 to perform a filling operation. The needle holding device 19 forms a holder for the filling needle 20. The needle holding device 19 may also be arranged in the filling apparatus 18 in such a way that it is moved by the filling apparatus 18 as part of the filling operation.

[0049] The isolation zone 12 includes a transfer system 22 via a partition wall 16 separating it from the operating zone 14. The transfer system 22 is used to transfer objects from the operating zone 14, particularly aseptically, into the isolation zone 12.

[0050] The transfer system 22 includes a replaceable β-component 24 and an α-port 27 fixedly disposed in the partition wall 16.

[0051] The replaceable β-assembly 24 is configured with a β-flange 26 (in Figure 1 (Partially shown transparently). The replaceable β-assembly 24 also includes a removable, correspondingly openable β-closure unit 30 (see, for example, see...). Figure 2 The β-closure unit 30 is designed in a quasi-cap-like manner.

[0052] The α-port 27, which is fixedly disposed in the partition wall 16, includes an α-flange 28 connected to the partition wall 16 and an α-closure unit 29 pivotally supported relative to the α-flange 28.

[0053] β-assembly 24 is configured to connect with α-port 27, which is fixedly disposed in partition wall 16. For connection, β-flange 26 is sealingly connected to α-flange 28. β-closure unit 30 is connected to α-closure unit 29 such that they abut against each other with their respective outer sides and can only move together. In the connected state, β-closure unit 30 and α-closure unit 29 form closure unit 31 of transfer system 22. In the closed state, α-closure unit 29 forms the side of closure unit 31 facing isolation zone 12, and β-closure unit 30 forms the side of closure unit 31 facing away from isolation zone 12. Closure unit 31 pivots into isolation zone 12 when opened.

[0054] To connect α-port 27 and β-assembly 24, they are connected to each other by means of a snap-fit ​​pin via the rotational movement of β-assembly 24. Thus, β-flange 26 is sealingly engaged with α-flange 28. Accordingly, β-closure unit 30 is sealingly engaged with α-closure unit 29. Other connection methods are also within the spirit of the invention.

[0055] The β-assembly 24 includes a receiving space 36 accessible via the β-closure unit 30, which is otherwise closed, and a housing 44 of the receiving space 36 detachable from the β-flange 26. In this example, the housing 44 is formed of a flexible plastic bag (also referred to as a β-bag). The housing 44 may also be formed of a dimensionally stable sterilizable container, such as a stainless steel container.

[0056] The β-closure unit 30, as part of the closure unit 31, opens and closes the receiving space 36 towards the isolation zone 12 in the assembled state. For this purpose, the β-closure unit 30 is designed as a circular, cap-like unit. The α-closure unit 29 is pivotally supported on the α-flange 28 via a hinge mechanism 45. The β-closure unit 30 is detachable from the β-flange 26 such that when connected to the α-closure unit 29, the β-closure unit 30 follows the latter's pivoting movement when opened. Figure 4 As can be easily seen, the transmission system 22 includes a locking mechanism 60. The locking mechanism 60 can only be unlocked when the α-closure unit 29 is connected to the β-closure unit 30.

[0057] To insert the filling needle 20 into the isolation zone 12, the filling needle 20 is first arranged in the β-assembly 24 in the receiving space 36. The filling needle 20 is connected to a tube 43, which extends from the receiving space 36 and includes a sterile connector 48 at its end opposite to the filling needle 20 for connection to the supply tank 46.

[0058] A retaining device 50 is arranged in the receiving space 36 of the β-assembly 24 to hold the filling needle 20 in a precise position. The retaining device 50 is arranged on the removable β-closure unit 30, such as... Figure 3 and Figure 4 As clearly shown. When the β-component 24 is connected to the α-port 27 and the closure unit 31 is opened, the filling needle 20 held in the holding device 50 moves into the isolation zone 12.

[0059] In this example, the manipulation device 40, arranged in the isolation zone 12, is designed as a robotic arm. The manipulation device 40 is configured to open the closing unit 31 (α-closing unit 29 and β-closing unit 30, which are connected to each other in the coupled state) and remove the filling needle 20 from the holding device 50 and insert it into the needle holding device 19. When the use of the filling needle 20 is completed, the filling needle 20 can be moved back into the holding device 50 by means of the manipulation device 40.

[0060] The filling system 10 includes an optional detection unit 42 configured for machine vision, and its field of view includes a transfer system 22, and in this example, a needle holding device 19, so that the position of the filling needle 20 can be detected by the detection unit 42 and the manipulation device 40 can be controlled and adjusted accordingly to remove the filling needle 20 from the holding device 50 and place it in the needle holding device 19, and after use, transfer it back to the holding device 50.

[0061] When the filling needle 20 is removed, the flexible bag-shaped housing 44 is compressed as the tube 43 is pulled into the isolation zone, as... Figure 2 As shown.

[0062] The housing 44 can also be designed as a half-size stable bellows unit. This type of housing 44 can be designed such that its extension toward the β-flange 26 is compressible and / or variable, but rigid transversely to the β-flange 26.

[0063] The closing unit 31 (or more precisely, the α-closing unit 29 and the β-closing unit 30 connected thereto) can be moved to a fixed open position during opening, such as Figure 2 As shown. In the fixed open position, the positions of α-closing unit 29, or more precisely the entire closing unit 31, including β-closing unit 30 and the retaining device 50 arranged thereon, are determined.

[0064] The filling needle 20 is connected via tube 43 to a supply tank 46 containing the medium 32 via a sterile connector 48. The supply tank 46 is in turn connected via a sterile connector 52 on the supply tank side to a tubing section passing through the peristaltic pump 56. A media filter 58 is arranged in the connecting line between the peristaltic pump 56 and the sterile connector 48 on the filling needle 20 side.

Claims

1. A β-component (24) of a delivery system (22), comprising a receiving space (36), a β-flange (26), a housing (44) defining the receiving space (36), and a β-closure unit (30), wherein, The β-closure unit (30) is detachably attached to the β-flange (26) for opening and closing the receiving space (36), and the β-flange (26) and the β-closure unit (30) are configured for coupling to the α-flange (28) and α-closure unit (29) of the α-port (27) of the delivery system (22), characterized in that the β-assembly (24) includes a retaining device (50) for retaining the filling needle (20) in a defined position and orientation, the retaining device being arranged on the side of the β-closure unit (30) facing the receiving space (36).

2. A sterile isolation area (12) having a partition wall (16), said sterile isolation area (12) being separated from a non-sterile operating area (14) by the partition wall (16), wherein, The partition wall (16) includes an α-port (27) of a transfer system (22) for introducing an object from the operating area (14) into the isolation area (12), wherein a filling device (18) is arranged in the isolation area (12), the filling device (18) being designed to fill a medium (32) into a sealable container (34) by means of a filling needle (20), characterized in that a β-component (24) according to claim 1 is coupled to the α-port (27), wherein when the closure unit (31) of the transfer system (22) formed by the interconnected α-closure unit (29) and β-closure unit (30) is opened, the holding device (50) is moved into the interior of the isolation area (12).

3. A filling system (10) having a sterile isolation area (12) according to claim 2, wherein, An operating device (40) is arranged in the isolation zone (12), the operating device (40) being designed to: open the β-closure unit (30) and α-closure unit (29) in the connected state, and / or remove the filling needle (20) held in the holding device (50) from the holding device (50), and / or place the filling needle (20) in the holding device (50).

4. The filling system (10) according to claim 3, characterized in that, The filling system includes a detection unit (42) configured for machine vision, and the field of view of the detection unit includes at least the transfer system (22), such that the position and / or orientation of the filling needle (20) can be detected by the detection unit (42).

5. The filling system (10) according to claim 3 or 4, characterized in that, The closure unit (31) formed by the interconnected α-closure unit (29) and β-closure unit (30) can be moved to a fixed open position during opening, in which the position of the closure unit (31) is determined.

6. The filling system (10) according to claim 3 or 4, characterized in that, The housing (44) of the receiving space (36) of the β-assembly (24) is designed to be detachable from the β-flange (26), and the housing (44) is formed of a flexible plastic bag or a dimensionally stable sterilizable container.

7. The filling system (10) according to claim 3 or 4, characterized in that, The filling needle (20) is connected to a tube (43) that extends out of the receiving space (36) and includes a sterile connector (48) at its end away from the filling needle (20) for connection to the supply tank (46).

8. The filling system (10) according to claim 7, characterized in that, The β-assembly (24) includes a return device for the tube (43), which also moves the tube (43) back into the receiving space during disassembly, i.e., when the filling needle (20) is moved back into the receiving space (36).

9. The filling system (10) according to any one of claims 3, 4, and 8, characterized in that, The β-flange of the β-assembly (24) and the α-flange (28) of the α-port (27) are adapted to be connected to each other by a snap fastener, and the β-closure unit (30) and the α-closure unit (29) are adapted to be connected to each other by a snap fastener.

10. A method of operating the filling system (10) according to any one of claims 3-9, characterized in that, The method includes the following steps: The β-assembly (24) is attached to the α-port (27) in the partition wall (16), wherein the filling needle (20) is located in the holding device (50) in the receiving space (36) of the β-assembly (24); A purification cycle is performed in the isolation zone (12); The transmission system (22) is opened by means of the operating device (40); The filling needle (20) is removed from the holding device (50) by means of the manipulation device (40); The filling needle (20) is placed in the needle holding device (19) of the filling device (18) by means of the manipulation device (40).

11. The method according to claim 10, characterized in that, The method further includes the following steps: The filling needle (20) is removed from the needle holding device (19) of the filling device (18) by means of the operating device (40); The filling needle (20) is placed in the holding device (50) by means of the manipulation device (40).

12. The aseptic isolation area (12) according to claim 2, characterized in that, The closure unit (31) formed by the interconnected α-closure unit (29) and β-closure unit (30) can be moved to a fixed open position during opening, in which the position of the closure unit (31) is determined.

13. The aseptic isolation area (12) according to claim 2 or 12, characterized in that, The housing (44) of the receiving space (36) of the β-assembly (24) is designed to be detachable from the β-flange (26), and the housing (44) is formed of a flexible plastic bag or a dimensionally stable sterilizable container.

14. The aseptic isolation area (12) according to claim 2 or 12, characterized in that, The filling needle (20) is connected to a tube (43) that extends out of the receiving space (36) and includes a sterile connector (48) at its end away from the filling needle (20) for connection to the supply tank (46).

15. The aseptic isolation area (12) according to claim 14, characterized in that, The β-assembly (24) includes a return device for the tube (43), which also moves the tube (43) back into the receiving space during disassembly, i.e., when the filling needle (20) is moved back into the receiving space (36).

16. The aseptic isolation area (12) according to any one of claims 2, 12, and 15, characterized in that, The β-flange of the β-assembly (24) and the α-flange (28) of the α-port (27) are adapted to be connected to each other by a snap fastener, and the β-closure unit (30) and the α-closure unit (29) are adapted to be connected to each other by a snap fastener.

17. The β-component (24) according to claim 1, characterized in that, The housing (44) of the receiving space (36) of the β-assembly (24) is designed to be detachable from the β-flange (26), and the housing (44) is formed of a flexible plastic bag or a dimensionally stable sterilizable container.

18. The β-component (24) according to claim 1 or 17, characterized in that, The filling needle (20) is connected to a tube (43) that extends out of the receiving space (36) and includes a sterile connector (48) at its end away from the filling needle (20) for connection to the supply tank (46).

19. The β-component (24) according to claim 18, characterized in that, The β-assembly (24) includes a return device for the tube (43), which also moves the tube (43) back into the receiving space during disassembly, i.e., when the filling needle (20) is moved back into the receiving space (36).

20. The β-component (24) according to any one of claims 1, 17, and 19, characterized in that, The β-flange of the β-assembly (24) and the α-flange (28) of the α-port (27) are adapted to be connected to each other by a snap fastener, and the β-closure unit (30) and the α-closure unit (29) are adapted to be connected to each other by a snap fastener.

Images