WO2024217944A1

WO2024217944A1 - Dosing apparatus for pharmaceutical purposes and method for operating a dosing apparatus

Info

Publication number: WO2024217944A1
Application number: PCT/EP2024/059637
Authority: WO
Inventors: Florian Barthelmess; Nico BUTZER; Oliver Lang; Philip MESSERSCHMIDT; Benjamin Spang
Original assignee: Bausch + Ströbel SE + Co. KG
Priority date: 2023-04-19
Filing date: 2024-04-09
Publication date: 2024-10-24
Also published as: DE102023109926A1

Abstract

The present invention relates to a dosing apparatus (100) for pharmaceutical purposes, comprising a closed container (104), which has a wall (126) and an interior (128) enclosed by the latter, at least one connection device (136, 142) for connecting the dosing apparatus (100) to a pharmaceutical facility (102) for processing an in particular liquid pharmaceutical product, wherein the at least one connection device (136, 142) is integrated in the wall (126) and comprises at least one closure element (138, 144) for selectively closing an opening (139, 145), a chassis (108) for moving the dosing apparatus (100) on a support surface (110), and at least one dosing tool (166) in the interior (128), which has a fluid line (168, 182) for guiding the product and a dosing unit (156) for dosing and/or conveying the product through the fluid line (168, 182), wherein the fluid line (168, 182) can be guided out of the interior (128) when the at least one closure element (138, 144) is opened. The present invention also relates to a method for operating a dosing apparatus (100).

Description

DOSING DEVICE FOR PHARMACEUTICAL PURPOSES AND METHOD FOR OPERATING A DOSING DEVICE

The present invention relates to a dosing device for pharmaceutical purposes, which can be used with a system for processing a product, in particular a filling machine for filling containers with a pharmaceutical product, wherein the dosing device is arranged externally to the system.

Furthermore, the present invention relates to a method for operating a dosing device of the type described above.

In the filling machine for filling the containers, a pharmaceutical substance is filled into pharmaceutical containers, which can be, for example, vials, syringes, cartridges or ampoules. The containers can be stable or non-stable. In the present example, the pharmaceutical product is in particular a fluid, specifically a liquid.

It is known that a dosing device is used with the filling machine, whereby the product is provided outside a chamber of the filling machine. A fluid line is fed through a defined connection device (for example an A/B port or RTP, rapid transfer port) and dosed into the containers in the filling machine. For example, a conveyor unit of the dosing device is used to dose the product. For example, the use of hose pumps (peristaltic pumps) is known, with which the liquid product can be dosed through a hose-shaped fluid line. In this context, the use of single-use equipment for the hose line, product containers and filling needles is known.

In practice, it is a challenge to comply with the hygienic requirements. Typically, the interior of the filling machine is operated with a high cleanliness class (e.g. GMP Type A), whereas the dosing device is located in an environment with a lower cleanliness class, for example GMP Type C.

The object of the present invention is to provide a dosing device for pharmaceutical purposes and a method for operating such a dosing device which can be used in a variety of ways, in particular with regard to compliance with hygiene requirements. This object is achieved by a dosing device according to the invention for pharmaceutical purposes, comprising a closed container which has a wall and an interior space enclosed by the latter, at least one connection device for connecting the dosing device to a pharmaceutical system for processing a particularly liquid pharmaceutical product, wherein the at least one connection device is integrated into the wall and comprises at least one closing element for selectively closing an opening, a chassis for moving the dosing device on a support surface and at least one dosing tool in the interior space, which has a fluid line for guiding the product and a dosing unit for dosing and/or conveying the product through the fluid line, wherein the fluid line can be led out of the interior space when at least one closing element is open.

The dosing device according to the invention has a closed container with an interior and chassis for moving the dosing device on a base. This makes it possible to prepare the dosing device for the intended use with the system for processing the product, in particular the filling machine. The dosing device can be equipped separately from the system, whereupon the dosing device is moved to the system and the fluid line is led from the interior of the container into the system via the open at least one closing element of the connection device. Alternatively, equipment can also be carried out directly at the site of use of the dosing device on the system. At least one dosing tool is provided in the interior, which comprises the fluid line and a dosing unit. The dosing unit allows the product provided to be dosed and/or conveyed in a targeted manner and thus introduced into the system through the fluid line.

As an alternative or in addition to the at least one connection device via which the fluid line can be led out of the interior, the dosing device can comprise at least one connector device, preferably in a standardized and/or sterile design. For example, the fluid line in the interior is connected to the connector device, and an external fluid line of the system can be connected to the connector device on the outside. The connector device means that the container does not need to be opened when the dosing device is connected to the system. The above design allows the dosing device to be preconfigured for the respective application. For example, pre-sterilized or decontaminated dosing tools can be introduced into the previously sterilized or decontaminated interior in order to meet the necessary hygiene requirements.

Alternatively or additionally, it is preferably conceivable that non-sterile or non-decontaminated dosing tools are introduced into the non-sterilized or non-decontaminated interior and that the interior, including the dosing tool accommodated therein, is subsequently sterilized or decontaminated.

The setup and in particular the introduction of dosing tools into the interior can be done in different ways. For example, a stationary chamber is operated, to which the mobile dosing device is docked and in which the dosing tool is accommodated. This can be sterile or decontaminated or otherwise non-sterile or non-decontaminated. After undocking, the dosing device can be driven to the system and used.

Alternatively or additionally, it can be provided, for example, that a mobile chamber in which the dosing tool is located is transported to the location of the dosing device and docked to it. After equipping, the mobile chamber is removed and the dosing device can be used on the system.

It is particularly advantageous if the dosing device is designed in such a way that existing dosing tools can be operated with the dosing device. Accordingly, the dosing device is preferably adaptable to different dosing systems, whereby, for example, different dosing units, fluid lines or other dosing tools of a known type can be used selectively. In the present case, a dosing tool can be considered to be an object that can be used to dose the product when the dosing device is used as intended, whereby the dosing tool can in particular have product contact.

Preferably, there is the possibility of multiple use of dosing tools.

The at least one connection device can be designed in different ways. For example, the use of a standardized port, in particular an A port or a B port, is conceivable. For example, an RTP (Rapid Transfer Port) is used for Docking to the system is used. All types of connection devices are conceivable, which specifically enable an aseptic connection of the system with the dosing device. The connection device can be single-walled, with one closing element, or multi-walled, for example double-walled with two closing elements.

With regard to compliance with hygiene requirements, it is advantageous if the container is or forms an isolating device, in particular with a defined atmosphere in the interior.

For example, the container may have a RABS feature (RABS, Restricted Access Barrier System).

The container is preferably liquid-tight and/or gas-tight when at least one connection device is closed.

The above properties allow in particular the use of the dosing device for processing highly active and/or toxic substances.

Conveniently, the degree of cleanliness in the interior can be set according to a specification, for example GMP Type A, B or C.

In order to provide and/or comply with the necessary hygiene requirements, it is advantageous if the dosing device can be decontaminated and/or sterilized in whole or in part, but at least in the interior, including objects accommodated therein and specially accommodated dosing tools.

For example, the dosing device has a decontamination device and/or a sterilization device in the interior. Sterilization can be carried out using steam, for example, and decontamination using H2O2.

For sterilization and/or decontamination via an external sterilization device and/or decontamination device, at least one connection element or transfer element can be present on the wall in order to introduce a medium into the interior. This makes it possible to save on an internal sterilization device and/or decontamination device. The at least one connection element allows the connection of a fluid line, the transfer element, for example, the passage of a fluid line. Alternatively or additionally, the connection element can be designed for docking a unit for decontamination or sterilization of material to be introduced, for example an autoclave, an F^Ch lock or a UV lock.

As a dosing tool, a fluid line and a dosing unit are accommodated in the interior, whereby more than one fluid line and/or more than one dosing unit can be provided.

The at least one dosing tool can further comprise at least one container for receiving the product, to which a fluid line is connected. The container can in particular be a bag.

Advantageously, the dosing device comprises a holding element in the interior for the defined arrangement and in particular hanging of the container.

The container and in particular bag can be a product bag or a batch bag.

The at least one dosing tool can comprise a filter element connected to the fluid line, in particular a sterile filter.

For example, the fluid line is connected to an outlet of the container, with the filter connected to the fluid line.

Overall, the equipment of the dosing device can depend on the user-specific and product-specific requirements and can preferably be adapted.

The dosing device can comprise a further fluid line as a dosing tool, wherein a feedthrough device for the further fluid line from the outside into the interior is arranged in the wall and the further fluid line is connected to an inlet of the container. Such an embodiment is used, for example, when two containers are used. For example, there is a preparation bag outside the container, from which the product is transferred through the further fluid line into the interior into a product bag received therein, from which the product is conveyed through the fluid line by means of the dosing unit. The feedthrough device is preferably designed to be sterile. This can, for example, be an aseptic liquid transfer port (SART or AT port).

The filter element can be connected to the additional fluid line inside the container or to the additional fluid line outside the container.

If, for example, only one fluid line is used, the dosing device can comprise a feedthrough device in the wall for feeding the fluid line from the outside into the interior, wherein the feedthrough device can be designed as described above. Such equipment is used, for example, with only one container. For example, the product bag is arranged outside the container to which the fluid line is connected.

From the above, it follows that the dosing device may comprise, outside the interior, a container for receiving the product, to which the further fluid line or the fluid line is connected.

The dosing device can, for example, comprise a holding element outside the interior for the defined arrangement and in particular hanging of the container. The holding element is preferably arranged and fixed on the container and can be moved together with it.

The at least one connection device and the feedthrough device can, for example, be arranged on opposite sides of the container.

The dosing device can preferably comprise a holder in the interior for detachable mounting of the dosing unit. When equipping the dosing device, for example, a suitable dosing unit can be introduced and mounted on the holder.

A connection element for providing electrical energy for the dosing unit is preferably arranged outside the interior. Alternatively or additionally, the dosing device can comprise an energy supply device.

A connection element for a control and/or signal line is preferably arranged outside the interior in order to control and/or regulate the operation of the dosing unit. An optional control device for the dosing device is conveniently arranged outside the interior.

Advantageously, at least one adapter element is provided for the detachable mounting of different dosing units on the holder. This enables a versatile design with regard to user-specific and product-specific requirements and a corresponding adaptation of the dosing device.

The dosing unit may be, for example, a peristaltic pump, a rotary piston pump, a time-pressure dosing unit and/or a multi-dosing unit.

It can be advantageous if the interior is divided into a first zone and a second zone by means of a dividing element, for example a partition wall, with the first zone having a higher degree of purity than the second zone. Separate zones can be provided, for example, to process products with special properties, for example toxic products.

For example, it can be provided that the fluid line is arranged in whole or in part and a filling needle connected to the fluid line is arranged in the first zone and/or that a container for holding the product is arranged in the second zone. The dosing unit can be arranged in the first zone or in the second zone, for example.

In one embodiment of the invention, at least one glove opening for a user can be provided on the container.

The wall is advantageously designed to be transparent, at least in sections, to allow a user to see into the container.

In a preferred embodiment of the invention, the at least one dosing tool can comprise at least one filling needle connected to the fluid line, which is arranged in the interior. When at least one connection device is open, the filling needle can be introduced into the system and used to fill the containers.

It can be provided that the dosing device comprises a holding part in the interior for the defined arrangement and in particular suspension of the filling needle. The holding part can be arranged, for example, on at least one closing element, which can be pivoted out of the interior when the at least one connection device is opened. This allows, for example, the filling needle to be moved into the interior of the system when the closing element is opened, so that it can be grasped there in an easier manner, for example by a robotic device and/or by hand.

The holding part can preferably be designed to be variable in size or length, whereby it can be transferred from a storage position to a use position in which the filling needle can be moved away from the container when at least one closing element is open. This improves the handling of the filling needle when it is being inserted or when it is being inserted into the interior of the system. The holding part can, for example, be telescopic, extendable, foldable or the like. A drive for the holding part can be provided. The use of a scissor pull or scissor grid on which the filling needle is held is conceivable.

The dosing device can comprise a further connection device integrated into the wall with at least one further closing element, wherein the connection devices are arranged, for example, on opposite sides of the container. The further connection device can be designed in a variety of ways. For example, the use of an A/B port, an RTP or similar is conceivable. An aseptic connection to the container is advantageously possible via the further connection device.

The additional connection device allows, for example, the dosing device to be connected to a stationary chamber. Alternatively or additionally, the use of a portable chamber is conceivable, which is brought to the dosing device and from which the dosing tool is removed.

The dosing device can comprise a gassing device which comprises a container for gas in the interior, a gas line connected to it and preferably a nozzle-shaped outlet element on this, wherein the gas line can be led out of the interior when at least one closing element is open. For example, this allows pre-gassing, filling gassing and/or post-gassing when filling the product. A separate gassing path can be saved in this way. In a preferred embodiment, the dosing device may comprise an air conditioning device for adjusting a temperature and/or a humidity content in the interior.

Alternatively or additionally, the dosing device can comprise a ventilation device for providing a preferably defined air flow in the interior. For example, a laminar air flow (LF) is provided. The ventilation device can be arranged in the interior or outside the interior, with the air flow taking place through an opening in the wall. The ventilation device can be designed as an overpressure device or as a negative pressure device.

The dosing device can comprise a weighing element arranged in the interior, the signal of which can preferably be used for dosing the product. For example, the holding element for the container is provided with a weighing element. The contents of the container or a change in the contents can be determined via the weight of the weighing element and the dosing can be determined and/or controlled as a result.

The dosing device can, for example, be operated manually by a user.

The chassis may be provided with a drive system.

In a favorable embodiment of the invention, it is provided that the dosing device is designed to be self-propelled and self-steering and can move independently, without the intervention of a user, over the installation surface. Accordingly, the dosing device can be designed to be robotic.

As mentioned above, the present invention also relates to a method.

A method according to the invention for operating a dosing device of the type described above comprises:

Providing the container;

- Connecting the container to a chamber in which at least one dosing tool is accommodated; Transferring the at least one dosing tool into the interior of the container and decoupling the dosing device from the chamber.

The advantages that have already been described in connection with the explanation of the metering device according to the invention can also be achieved by carrying out the method. In this regard, reference is made to the above explanations.

Advantageous embodiments of the method result from advantageous embodiments of the metering device according to the invention. Reference is made to the above explanations.

The chamber can be stationary, with the dosing device being moved to the chamber and connected to it. Alternatively, a mobile chamber can be provided which is brought to the dosing device and connected to it.

The procedure may, for example, include the following further steps:

- Connecting the container to a pharmaceutical plant for processing the product;

Removing at least one fluid line and transferring it to the system;

Operating the dosing unit to supply the product.

The following description of preferred embodiments of the invention serves to explain the invention in more detail in conjunction with the drawing. They show:

Figure 1: a schematic perspective representation of the dosing device according to the invention in a preferred embodiment when used in a system for processing a pharmaceutical product;

Figure 2: the dosing device in a partial view, cut open;

Figure 3: a plan view of the dosing device, cut open;

Figure 4: a representation corresponding to Figure 2 with an alternative use of the dosing device; Figure 5: the dosing device in a representation corresponding to Figure 2 in an alternative application;

Figure 6: the dosing device according to Figure 2 in an alternative application;

Figure 7: a perspective view of an embodiment of a holding part for a filling needle and a fluid line of the dosing device according to the invention;

Figure 8: a representation of a further preferred embodiment of a holding part for a filling needle and a fluid line of the dosing device according to the invention;

Figure 9: a schematic representation of variants of a setup process for equipping the dosing device according to the invention;

Figure 10: another step in equipping the dosing device; and

Figure 11: another step in equipping the dosing device.

The drawing shows an advantageous embodiment of the dosing device according to the invention, designated overall by the reference numeral 100, with which the method according to the invention can be carried out according to a preferred embodiment.

The dosing device 100 is versatile and is used with a system 102 for processing a pharmaceutical product. The product in this case is a liquid that can be provided by means of the dosing device 100 and, in particular, introduced into the system 102 in a dosed manner. In the system 102, pharmaceutical containers are filled with the product, for example vials, syringes, cartridges or ampoules. The system 102 comprises a wall 103.

The dosing device 100 can be adapted in a variety of ways depending on the requirements, user-specific and product-specific, depending on the product to be processed. It is particularly advantageous here that various hygienic requirements can be met. Preferably, different degrees of purity can be achieved, for example GMP type A, B or C. It is preferably possible to design the dosing device with the container as an isolating device with a defined atmosphere in the interior. The container can have a RABS property and in particular be liquid-tight and/or gas-tight when closed.

Overall, the dosing device 100 forms in particular a closed containment which is mobile, in the present case can be moved on the installation surface 110 and can be moved towards and away from the system 102.

Figures 1 to 3 show the dosing device 100 with an exemplary equipment and are explained below.

The dosing device 100 comprises a container 104. In the present case, the container 104 is arranged on a substructure 106, for example in the form of a frame. A chassis 108 for moving on a support surface 110 is arranged on the substructure 106. In the present case, the chassis 108 comprises rollers 112 that are not driven. In the present example, the dosing device 100 can be moved manually on the support surface 110 by a user 114.

Alternatively or additionally, it is conceivable that the chassis 108 has a drive 116.

Alternatively or additionally, it is conceivable that the dosing device 100 is designed to be self-propelled and self-steering and can be moved autonomously on the installation surface 110 in a robotic manner.

To control and/or regulate the operation of the dosing device 100, for example during autonomous operation, a control device 118 is provided, which is conveniently arranged outside the container 104.

For example, the control device 118 is accommodated in a housing 120 which is held on the base 106.

For example, a power supply device 122 can be accommodated in the housing 120. Outside the container 104, for example on the base 106 or on the housing 120, alternatively or additionally, for example, a connection element 124 for connecting an external energy supply device can be arranged.

In the present embodiment, the container 104 is cuboid-shaped, although this is not restrictive. The container 104 comprises a wall 126 that encloses an interior space 128. The wall 126 can be completely or partially transparent to allow the user 114 to see into the interior space 128.

The container 104 may comprise a removable wall or a removable section of a wall (for example in the manner of a removable or hinged lid) in order to open the container and access the interior space 128.

The dosing device 100 can comprise at least one glove opening 130 on the container 104, via which the user 114 can reach into the interior 128 in a sterile manner. In the present case, two glove openings 130 are provided as an example. The wall 126 is advantageously transparent in the wall that accommodates the glove openings 130.

The dosing device 100 can be connected to the system 102 and can be connected in particular aseptically. For this purpose, a connection device 132 with an inwardly opening closing element 134 is provided on the system 102.

The dosing device 100 is positioned on the system 102 such that a connection device 136 integrated into the wall 126 with a closing element 138 comes to coincide with the connection device 132. The closing element 138 can be opened to expose an opening 139 in the wall 126, and in this case it can preferably be pivoted into the interior 140 of the system 102. In this way, the interior 128 can communicate with the interior 140.

The connection devices 132, 136 are preferably standardized, for example designed as A/B ports or as RTP ports.

The dosing device 100 can comprise a further connection device 142 which is integrated into the wall 126. Such a connection device 142 is shown in the drawing, wherein the connection devices 136, 142 are arranged on opposite sides of the wall 126. This can be done, for example, as a advantageous for handling the dosing device 100 to maintain a defined work process. It can be provided that dosing tools are introduced into the interior 128 from one side via the connection device 142 and are removed from the opposite side via the connection device 136.

The connection device 142 also comprises a closing element 144. When the closing element 144 is open, an opening 145 in the wall 126 is exposed.

The connection device 142 is preferably designed in a standardized manner, for example as an A/B port, for example as an RTP port.

In the present embodiment, the dosing device 100 comprises a feedthrough device 147 that is integrated into the wall 126. A fluid line can be guided in a sterile manner from the outside to the inside into the interior 128 through the feedthrough device 147. For example, the feedthrough device 147 is designed in a standardized manner, for example as an aseptic liquid transfer port (SART or AT port).

Dosing tools for dosing the product, in particular the liquid product, can be accommodated in the interior 128. It is provided that at least one dosing unit and at least one fluid line are accommodated. The dosing tools can comprise, for example, the following, in particular in the interior 128: at least one dosing unit, at least one fluid line, at least one container for the product, at least one filter element, at least one filling needle that is connected to the fluid line. Various types of equipment of the dosing device 100 are discussed below.

First, however, other optional features of the dosing device will be presented as examples.

A sterilization device 148, a decontamination device 150, a ventilation device 152 and an air conditioning device 154 may be provided.

The devices 148, 150, 152 and 154 can be arranged entirely or partially in the interior 128 or entirely or partially outside the container 104. Figure 3 shows the devices 148, 150, 152 and 154 in the interior 128 by way of example. When arranged outside the container 104, at least one connection element or the like may be provided in order to pressurize the interior space 128 in the desired manner.

The sterilization device 148 and the decontamination device 150 enable, for example, sterilization or decontamination of the interior 128 and the material arranged therein, in particular the dosing tools. Steam or H2O2 can be used for sterilization or decontamination, for example.

A defined flow, for example a laminar flow, can be generated in the interior space 128 via the ventilation device 152.

For example, the temperature and/or a degree of humidity in the interior 128 can be adjusted via the air conditioning device 154.

The devices 148, 150, 152 and 154 are preferably connected to the control device 118 for controlling and/or regulating the operation.

As can be seen in particular from Figures 1 to 3, a dosing unit 156 is arranged in the interior 128, which is designed as a peristaltic pump 158 in the present case. To drive the dosing unit 156, a drive unit 160 can be arranged in the interior 128 or guided into it, preferably in a pharmaceutically compatible design. The drive unit 160 is supplied with electrical energy, for example, by means of the energy supply device 122 or externally via the connection element 124.

Conveniently, the drive unit 160 forms a receptacle 162 to which various dosing units 156 can be detachably mounted, depending on the use of the dosing device 100. For example, a respective adapter element 164 is provided in order to adapt the respective dosing unit 156.

The dosing unit 156 is in this case a dosing tool 166 which is used for dosing and/or conveying the liquid product.

As a further dosing tool 166, a fluid line 168 is provided in the interior 128, which is designed in particular as a hose line and which is inserted into the peristaltic pump 158. A filling needle 170 connected to the fluid line 168 is provided as a further dosing tool 166. The product can be filled into the containers via the filling needle 170.

In the present case, a container 172 in the form of a bag 174 is provided as a further dosing tool 166. The fluid line 168 is connected to an outlet of the bag 174, guided through the peristaltic pump 158 and has the filling needle 170 at the end.

For the defined arrangement of the filling needle 170 in the interior space 128, the dosing device 100 comprises a holding part 176. For example, the filling needle 170 is held on the holding part 176 by force and/or form locking.

It may be advantageous if the holding part 176 is fixed to the closing element 138. When the closing element 138 is opened, the holding part 176 with the filling needle 170 held thereon is moved into the interior 128 of the system 102 and can therefore be gripped in an easier manner.

A holding element 178 for the defined arrangement of the bag 174 is preferably arranged in the interior 128. In the present case, the holding element 178 is fixed to the wall 126, and the bag 174 is suspended from the holding element 178.

For example, a weighing element 180 can be provided on the holding element 178, which weighing element 180 is designed as a beam balance. This makes it possible in particular to determine a change in the mass of the bag 174 and thereby control and/or regulate the dosing process. The weighing element 180 can be coupled to the control device 118.

As a further dosing tool 166, the dosing device 100 in the present example comprises a further fluid line 182, which is designed as a hose line. The fluid line 182 is connected to an inlet of the bag 174, wherein it is guided from the outside through the feedthrough device 147 into the interior 128.

A filter element 184, which is in particular a sterile filter, is connected to the fluid line 182 as a further dosing tool 166. The filter element 184 is arranged in the interior space 128 in the present case. The further fluid line 182 is connected to the outlet of a further container 186, which in this case is designed as a bag 188.

For the defined arrangement of the bag 188, the dosing device 100 comprises a holding element 190. In the present example, the bag 188 can be suspended from the holding element 190. The holding element 190 is preferably fixed to the container 104.

In the present exemplary configuration of the dosing device, the bag 188 serves as a base for storing the product. The product passes through the fluid line 182 into the bag 174, which serves as a product bag. Starting from the bag, the product passes through the fluid line 168 to the filling needle 170 and can be filled into the containers.

The dosing device 100 is positioned on the system 102 when in use. The connection devices 132, 136 are aligned in order to dock the dosing device 100. When the closing elements 134, 138 are open, the fluid line 168 with the filling needle 170 can be introduced into the interior 128. This is shown in dashed lines in Figure 2. The filling needle 170 can be grasped, for example, by a robotic device or by a user.

Figures 4 to 6 show different types of equipment for the dosing device 100, such as can be used, for example, when processing a different product or for different user requirements. Only the differences compared to the equipment according to Figures 1 to 3 are explained.

In the equipment variant according to Figure 4, the filter element 184 is also connected to the fluid line 182, but is arranged outside the container 104.

In the equipment variant according to Figure 5, the bag 174 in the interior 128 is omitted. Instead, only the outer bag 188 is present as a product bag. Only the fluid line 168 is used, which is led from an outlet of the bag 188 through the feedthrough device 147 and into which the filter element 184 is connected.

In the equipment variant according to Figure 6, the outer bag 188 is omitted. The fluid line 182 is omitted. The fluid line 168, into which the filter element 184 is connected, is connected to the outlet of the bag 174 as in the variant according to Figures 1 to 3. Figure 7 shows an embodiment of the holding part 176 which is designed to be variable in length. A view from the side of the system 102 is shown, in which the filling needle 170 has already been introduced into the interior space 128.

The holding part 176 is designed to be foldable and, in the present example, comprises three segments 192, 193, 194. The segments 192, 193 are pivotally connected to one another at a joint 195. In a corresponding manner, the segments 193 and 194 are pivotally connected to one another at a further joint 196.

The filling needle 170 is presently held on the segment 194, and the fluid line 168 is guided along the holding part 176.

Figure 7 shows the unfolded position of the holding part 176. As long as the holding part 176 is arranged in the closed container 104, the holding part 176 is folded together (not shown). To unfold or fold the holding part 176, the segments 192 to 194 can be pivoted relative to one another.

The dosing device 100 can comprise a gassing device 198, which is preferably arranged in the interior 128 and can be controlled, for example, by the control device 118 (Figure 3). The gassing device 198 can be designed for pre-gassing, intermediate gassing and/or post-gassing of the container to be filled.

The gassing device 198 can, for example, comprise a container 200 for gas, a gas line 202 and at least one outlet element 204 which is nozzle-shaped.

Figure 7 shows schematically an outlet element 204. The outlet element 204 is held on the segment 194.

Two outlet elements 204 are shown in the embodiment of the holding part 176 according to Figure 8.

In the variant according to Figure 8, the outlet elements 204 as well as the filling needle 170 are held on a holding member 206 of the holding part 176. The holding member 206 is here fixed at the end to an extension member 208, which in this example is a scissor pull 210 The scissor hoist 210 is shown in Figure 8 in the extended position in which it projects into the interior 128 of the system 102.

In the retracted position not shown in the drawing, the scissor pull 210 is arranged in a receptacle 212 within the opening 139, so that the holding member 206 is also positioned within the container 104 when the closing element 138 is closed.

Figures 9 to 11 schematically show a setup process for equipping the dosing device 100 according to the task to be performed. The equipment variant shown in Figure 5 and already explained is shown as an example.

To equip the dosing device 100, various types of chambers 214, 216, 218 can be connected to the container 104, in particular the connection device 142. The chambers 214, 216, 218 advantageously comprise a connection device for a preferably aseptic connection, which can be aseptically coupled to the connection device 142.

In the present case, the chambers 214, 216, 218 differ in that the respective contents of dosing tools 166 are different. It is assumed here that the dosing unit 156, for example the peristaltic pump 158, is already located in the interior 128 of the container 104.

The chamber 214, which is used in the assumed example and whose contents are or were introduced into the container 104 in Figures 10 and 11, contains the fluid line 168 with the filling needle 170 and the filter element 184. After docking (Figure 10), these dosing tools 166 are introduced into the interior 128 and then the chamber 214 is uncoupled. The fluid line 168 is guided through the feedthrough device 147 and connected to the bag 188 (Figure 11).

For an equipment variant not explained below, for example, the chamber 216 can be used in which, in addition to the aforementioned dosing tools 166, the dosing unit 156 is introduced into the interior 128 as a further dosing tool.

In an equipment variant that is also not explained in more detail, the bag 174 is additionally introduced into the interior space 128 via the chamber 218. In this example, the fluid line 168 remains in the interior space 128, for example. Figures 9 to 11 show the chambers 214 to 218 in a movable form, which are moved to the dosing device 100. The chambers 214 to 218 are designed to be movable, are connected to the dosing device 100 and then removed from it again.

In the illustration shown, the dosing device 100 is already positioned in the desired position on the system 102, although the closing elements 134, 138 are not yet open. It is understood that the dosing device 100 can be positioned at a distance from the system 102 during the equipment processes.

Alternatively or in addition to the mobile chambers 214 to 218, it is conceivable that the dosing device 100 is moved on the installation surface 110 of a stationary chamber 220 in which the dosing tools 166 are accommodated and which is shown schematically in Figure 9.

Depending on the application, it may be provided that the dosing tools 166 to be introduced are already sterilized or decontaminated or that the sterilization or decontamination only takes place in the interior space 128.

For example, the following steps are conceivable when operating the dosing device 100:

Provision of pre-sterilized dosing tool (single-use) 166 via an RTP or another type of connection device in the previously sterilized or decontaminated chamber 214 to 220, installation through the glove openings 130 by the user 114, closing and undocking of the container 104, connection to the system 102, opening the connection device 132, 136, insertion of the filling needle(s) 170 and start of filling;

Inserting non-sterile dosing tool 166 into the non-sterilized or non-decontaminated container 104, installing the dosing tool 166, closing the container 104 and sterilizing or decontaminating at least the interior 128 with contents, connecting to the system 102, opening the connection device 132, 136, inserting the filling needle(s) 170 and starting the filling process; Docking of the container 104, which has previously been sterilized or decontaminated on the inside, to a sterile external chamber or setup unit 214 to 220 via a connection device, installation through glove openings 130 of the external chamber or setup unit 214 to 220, closing and undocking of the container 104, connection to the system 102, opening the connection device 132, 136, insertion of the filling needle(s) 170 and start of filling;

Docking of the non-sterilized or decontaminated container 104 to a non-sterile chamber or external setup unit 214 to 220 via a connection device, sterilization or decontamination of the container 104 and the chamber or setup unit 214 to 220 together, installation of the dosing tool 166 through glove openings of the chamber or external setup unit 214 to 220, closing and undocking of the connection device, connection to the system 102, opening the connection device 132, 136, insertion of the filling needle(s) 170 and start of filling;

Docking the non-sterilized or decontaminated container 104 to a non-sterile chamber or external setup unit 214 to 220 via a connection device, installation of the dosing tool 166, sterilization or decontamination of at least the interior 128 with contents, closing and undocking the connection device, connection to the system 102, opening the connection device 132, 136, insertion of the filling needle(s) 170 and start of filling.

It proves to be advantageous that the container 104 can maintain its hygienic properties for a longer period of time. For example, the dosing device 100 can be prepared and stored or temporarily parked sufficiently long before use, with it only being moved to the system 102 at a later time.

Figure 3 shows an optionally present separating element 224 in the interior space 128 via a dashed line 222. The separating element 224 can, for example, be a partition wall 226 with at least one opening.

The interior space 128 is divided into a first zone 228 and a second zone 230 via the separating element 224, wherein the first zone 228 has a higher purity class than the second zone 230. In the present example, the fluid line 168, the filling needle 170 and the dosing unit 156 are arranged in the first zone 228. The fluid line 168 is guided through the separating element 224 into the second zone 230, in which the bag 174 and the filter element 184 are arranged.

The interior space 128 can have different degrees of purity depending on the requirements. For example, a degree of purity of GMP A for highly active and toxic substances is conceivable. On the other hand, a degree of purity of GMP B or GMP C is conceivable. It is advantageous that the respective degree of purity can be achieved as required for the dosing device 100 depending on the application, which makes the dosing device 100 particularly versatile.

list of reference symbols

Dosing device System Wall Container Substructure Chassis Installation surface Roller User Drive Control device Housing

Energy supply device connection element wall, 140 interior

Glove opening , 136, 142 Connection device , 138, 144 Closing element , 145 Opening

Implementation device Sterilization device Decontamination device Ventilation device Air conditioning device Dosing unit Peristaltic pump Drive unit , 212 Recording

Adapter element dosing tool, 182 fluid line

filling needle container , 188 Bag holding part , 190 Holding element Weighing element Filter element Container , 193, 194 Segment , 196 Joint

Gassing device Container Gas line Outlet element Holding element Extraction element Scissors pull , 216, 218 Chamber Stationary chamber Dashed line Separating element Partition wall First zone Second zone

Claims

PATENT CLAIMS

1 . Dosing device (100) for pharmaceutical purposes, comprising a closed container (104) which has a wall (126) and an interior space (128) enclosed by the latter, at least one connection device (136, 142) for connecting the dosing device (100) to a pharmaceutical system (102) for processing a particularly liquid pharmaceutical product, wherein the at least one connection device (136, 142) is integrated into the wall (126) and comprises at least one closing element (138, 144) for selectively closing an opening (139, 145), a chassis (108) for moving the dosing device (100) on a support surface (110) and at least one dosing tool (166) in the interior space (128) which has a fluid line (168, 182) for guiding the product and a Dosing unit (156) for dosing and/or conveying the product through the fluid line (168, 182), wherein the fluid line (168, 182) can be led out of the interior space (128) when at least one closing element (138, 144) is open.

2. Dosing device (100) according to claim 1, characterized in that at least one of the following applies: the container (104) is or forms an isolator device, in particular with a defined atmosphere in the interior (128); the container (104) has a RABS property; the container (104) is liquid-tight and/or gas-tight.

3. Dosing device (100) according to claim 1 or 2, characterized in that the at least one dosing tool (166) further comprises at least one of the following: a container (172) for receiving the product, to which the fluid line (168, 182) is connected, wherein the container (172) is in particular a bag (174, 188), wherein the dosing device (100) is preferably in Interior (128) comprises a holding element (178, 190) for the defined arrangement and in particular suspension of the container (172); a filter element (184), in particular a sterile filter, connected in the fluid line (168, 182), wherein the fluid line (168, 182) is preferably connected to an outlet of the container (172) and the filter is connected in the fluid line (168, 182).

4. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises a further fluid line (168, 182) as a dosing tool (166), wherein a feedthrough device (147) for the further fluid line (168, 182) from the outside into the interior (128) is arranged in the wall and the further fluid line (168, 182) is connected to an inlet of the container (172), wherein preferably the filter element (184) is connected in the interior (128) or outside the container (104) into the further fluid line (168, 182).

5. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises a feedthrough device (147) in the wall (126) for feeding the fluid line (168, 182) from the outside into the interior (128).

6. Dosing device (100) according to claim 4 or 5, characterized in that the dosing device (100) comprises, outside the interior (128), a container (172) for receiving the product, to which the further fluid line (168, 182) or the fluid line (168, 182) is connected, wherein the dosing device (100) comprises, in particular outside the interior (128), a holding element (178, 190) for the defined arrangement of the container (172), wherein the holding element (178, 190) is preferably arranged or fixed on the container (104).

7. Dosing device (100) according to one of the preceding claims, characterized in that the at least one connection device (136, 142) and the feedthrough device (147) are arranged on opposite sides of the container (104).

8. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) in the interior (128) comprises a receptacle (162, 212) for detachable mounting of the dosing unit (156), wherein preferably at least one adapter element (164) is provided for detachable mounting of different types of dosing units (156) on the receptacle (162, 212).

9. Dosing device (100) according to one of the preceding claims, characterized in that a peristaltic pump (158), a rotary piston pump, a time-pressure dosing unit and/or a multi-dosing unit is provided as the dosing unit (156).

10. Dosing device (100) according to one of the preceding claims, characterized in that the interior (128) is divided into a first zone (228) and a second zone (230) by means of a separating element (224), wherein the first zone (228) has a higher degree of purity than the second zone (230), wherein the separating element (224) is in particular a partition wall (226).

11. Dosing device (100) according to claim 10, characterized in that the fluid line (168, 182) in whole or in part and a filling needle (170) connected to the fluid line (168, 182) are arranged in the first zone (228) and/or that a container (172) for receiving the product is arranged in the second zone (230).

12. Dosing device (100) according to one of the preceding claims, characterized in that at least one glove opening (130) for a user (114) is provided on the container (104).

13. Dosing device (100) according to one of the preceding claims, characterized in that the at least one dosing tool (166) comprises at least one filling needle (170) connected to the fluid line (168, 182) and arranged in the interior (128).

14. Dosing device (100) according to claim 13, characterized in that at least one of the following applies: the dosing device (100) comprises a holding part (176) in the interior (128) for the defined arrangement and in particular suspension of the filling needle (170); the holding part (176) is arranged on at least one closing element (138, 144) which can be pivoted out of the interior (128) when the at least one connection device (136, 142) is opened.

15. Dosing device (100) according to claim 13 or 14, characterized in that the holding part (176) is designed to be variable in size or length and can be transferred from a storage position into a use position in which the filling needle (170) can be brought into a distance from the container (104) when at least one closing element (138, 144) is open.

16. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises a further connection device (136, 142) integrated into the wall (126) with at least one further closing element (138, 144), wherein the connection devices (136, 142) are arranged in particular on opposite sides of the container (104).

17. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises a gassing device (198) which comprises a container (172) for a gas in the interior (128), a gas line (202) connected thereto and preferably a nozzle-shaped outlet element (204) on the latter, wherein the gas line (202) can be led out of the interior (128) when at least one closing element (138, 144) is open.

18. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) is decontaminated and/or sterilized and/or that the dosing device (100) has a decontamination device (150) and/or a sterilization device (148) in the interior (128).

19. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises an air conditioning device (154) for adjusting a temperature and/or a humidity content in the interior (128).

20. Dosing device (100) according to one of the preceding claims, characterized in that the dosing device (100) comprises a ventilation device (152) for providing a preferably defined air flow in the interior space (128).

21. Dosing device (100) according to one of the preceding claims, characterized in that at least one of the following applies: the dosing device (100) is manually guided; the chassis (108) has a travel drive (118); the dosing device (100) is designed to be self-propelled and self-steering.

22. A method for operating a dosing device according to any one of the preceding claims, comprising:

Providing the container (104);

Connecting the container (104) to a chamber (214, 216, 218, 220) in which at least one dosing tool (166) is accommodated;

Transferring the at least one dosing tool (166) into the interior (128) of the container (104) and decoupling the dosing device (100) from the chamber (214, 216, 218, 220).

23. Method according to claim 22, comprising the further method steps:

Connecting the container (104) to a system (102) for processing a pharmaceutical product, in particular a liquid one;

Removing the at least one fluid line (168, 182) and transferring it into the system (102);

Operating the dosing unit (156) to supply the product.