Dispensing kit cooperating with a dispensing device for a system to produce a plurality of radiopharmaceutical batches

Abstract

Dispensing kit (6) cooperating with a dispensing device (5) for a radiopharmaceutical batch production system (1), the dispensing kit (6) having: a cassette (7) mountable on the dispensing device (5) and provided with a control hydraulic circuit (32); a tank (8) for the radiopharmaceutical, communicating with control hydraulic circuit (32); a needle assembly (9) having a needle (33) communicating with the control hydraulic circuit (32) and insertable into a container (4) to introduce a dose of radiopharmaceutical into it; a needle holder element (34) and a cap (35) couplable with each other to separate the needle (33) from the external environment when the needle (33) is not used for dispensing the radiopharmaceutical; and a conduit (39) communicating with the bottom of the cap (35) and acting as a drain when the cap (35) is coupled to the needle holder element (34) for a flushing of the dispensing kit (6). The dispensing device (5) has a movable clamp (65) and a handling device (67) for removing the cap (35) from the needle holder element ( 34 ).

Description

[0001] "DISPENSING KIT COOPERATING WITH A DISPENSING DEVICE FOR A SYSTEM TO PRODUCE A PLURALITY OF RADIOPHARMACEUTICAL BATCHES"

[0002] Cross-Reference to Related Applications

[0003] This Patent Appl ication claims priority from Italian Patent Application No . 102024000015004 filed on June 28 , 2024 , the entire disclosure of which is incorporated herein by reference .

[0004] Technical field

[0005] The present invention relates to a dispensing kit for a dispensing device to dispense a radiopharmaceutical in at least one container, to a dispensing device cooperating with one or more dispensing kits , and to a radiopharmaceutical production system comprising the dispensing device and a plurality of dispensing kits for producing a plurality of batches of radiopharmaceutical in sequence .

[0006] In particular, the present invention finds advantageous , but not exclusive application in a production line of liquid radiopharmaceuticals , for example a so-called radiopharmacy, to which the following description will make explicit reference without thereby losing in generality .

[0007] Context

[0008] A batch of a radiopharmaceutical is a set of containers , typically vials , bottles or syringes , filled with the same radiopharmaceutical having a speci fic production history . This means that , in general , some production batches , although they are of the same radiopharmaceutical , can be di f ferentiated even only in terms of di f ferent production periods or circumstances .

[0009] The typical approach known for the production of a batch of a liquid radiopharmaceutical provides for the following steps : bringing into a work area, normally the work chamber of a pharmaceutical isolator, all the sterile and still packaged material s necessary for the production of a batch, such as the bottles to be filled with respective doses of radiopharmaceutical and at least one single-use dispensing kit ; decontaminating the work area to ensure that the sterile condition of the radiopharmaceutical is maintained during dispensing; removing the materials from the bags and setting them up in the work area ; filling the bottles with the radiopharmaceutical and extracting the bottles from the work area ; and cleaning the work area, removing all the materials used for the production of the batch . At this point , the production of a new batch can begin by repeating all the steps described above .

[0010] The cleaning step of the work area is necessary to avoid cross-contamination between di f ferent batches . The singleuse dispensing kit used for a certain production batch cannot remain in the work area together with the single-use dispensing kit to be used for the subsequent production batch . In fact , the single-use dispensing kit of known type is an open system, i . e . it has surfaces that come into contact with the radiopharmaceutical and that are also exposed to the external environment . Therefore , at the end of the production of a batch of a radiopharmaceutical , the exposed surfaces show traces of this batch of radiopharmaceutical and could release particles or residues into the environment that are potentially contaminating for the batch of radiopharmaceutical produced subsequently . In this regard, the most exposed and most contaminating part of the single-use di spensing kit is the needle that is used to dispense the radiopharmaceutical into the bottles .

[0011] The approach described above implies a waiting time between the production of one batch and the next which limits the daily production capacity . This approach is less and less compatible with the growing market demand for radiopharmaceuticals that entails the need to produce more batches per day .

[0012] Summary

[0013] Aim of the present invention is to realise a single-use dispensing kit to be used inside a pharmaceutical isolator during the production of a batch of radiopharmaceutical , which is free from the drawbacks described above and, at the same time , is easy to use and cheap to manufacture .

[0014] In accordance with the present invention there are provided, a dispensing kit for a dispensing device to dispense a radiopharmaceutical in at least one container, a dispensing device for dispensing a radiopharmaceutical in at least one container, and a radiopharmaceutical production system to produce a plurality of batches of radiopharmaceutical , as defined in the appended independent claims .

[0015] Further features of the present invention are contained in the dependent claims .

[0016] The claims describe preferred embodiments of the present invention to be considered as an integral part of the present disclosure .

[0017] Brief description of the drawings

[0018] The present invention will now be described with reference to the attached drawings , which show a non-limiting embodiment thereof , wherein :

[0019] Figure 1 shows a radiopharmaceutical production system reali zed according to the present invention;

[0020] Figure 2 shows a dispensing kit set up in the radiopharmaceutical production system of Figure 1 and reali zed according to the present invention;

[0021] - Figure 3 shows an inner part of a cassette of the dispensing kit of Figure 2 ; and

[0022] - Figure 4 shows a control module of a dispensing device of the radiopharmaceutical production system of Figure 1 ; and

[0023] - Figures 5 to 17 show a part of the dispensing device of the radiopharmaceutical production system of Figure 1 during subsequent operating steps .

[0024] Description of embodiments

[0025] In Figure 1 , 1 generically denotes , as a whole and with some parts not shown for illustrative simplicity, a radiopharmaceutical production system, of the type that can be integrated into a larger radiopharmaceutical production line (not shown) , to produce a plurality of batches of radiopharmaceutical .

[0026] The radiopharmaceutical production system 1 comprises an isolator, for example a pharmaceutical isolator, of which the inside of a relative work chamber 2 is essentially shown . The insulator is of the type shielded against ioni zing radiation . The radiopharmaceutical production system 1 comprises a support 3 , for example of the staircase type , positionable in the work chamber 2 to orderly arrange a plurality of empty containers 4 , a dispensing device 5 arranged in the work chamber 2 , and a plurality of dispensing kits 6 , each of which is associated with a respective batch of radiopharmaceutical and is set up in the work chamber 2 so as to cooperate with the dispensing device 5 to produce the batch of radiopharmaceutical as a set of doses of radiopharmaceutical contained in respective containers 4 .

[0027] In the example shown by the figures , each container 4 consists of a bottle of the type comprising a rubber plug and a metal ferrule . According to alternative embodiments not shown, each container 4 consists of a vial , a bottle or a syringe .

[0028] Each dispensing kit 6 comprises a cassette 7 , a tank 8 for a bulk liquid radiopharmaceutical and a needle assembly 9 comprising a needle (not visible in Figure 1 ) to introduce a dose of radiopharmaceutical into a container 4 when the latter is suitably positioned in the dispensing device 5 .

[0029] The dispensing device 5 comprises a frame 10 resting on a floor 11 of the work chamber 2 , a plurality of control modules 12 integral with the frame 10 and comprising respective peristaltic pumps 13 . The number of the dispensing kits 6 set up is equal to the number of the control modules 12 . The cassette 7 of the respective dispensing kit 6 is releasably mounted on each control module 12 . The dispensing device 5 comprises a support body 14 configured to receive and support the needle assembly 9 and a handling device 15 to move the container 4 between an insertion position, wherein one of the containers 4 can be inserted or withdrawn into or from the dispensing device 5 , and a filling position, wherein the needle of the needle assembly 9 allows the container 4 to be filled, as will be better explained below . Figure 1 shows a container 4 in the insertion position .

[0030] The radiopharmaceutical production system 1 comprises a support 16 arranged in the work chamber 2 , in particular mounted on the floor 11 , for receiving and supporting the tanks 8 . In particular, the support 16 comprises a plurality of seats 17 , each of which is adapted to receive a respective tank 8 . The support 16 is adapted to rotate around an axis (not shown) perpendicular to the floor 11 and the seats 17 are arranged around this axis .

[0031] The radiopharmaceutical production system 1 comprises a further support 18 arranged in the work chamber 2 , in particular mounted on the floor 11 , for receiving and supporting the needle assemblies 9 . In particular, the support 18 compri ses a plurality o f seats 19 , each of which is adapted to receive a respective needle assembly 9 . The support 18 is adapted to rotate around a further axis (not shown) perpendicular to the floor 11 and the seats 19 are arranged around this further axis .

[0032] The radiopharmaceutical production system 1 comprises a further support 20 for supporting a plurality of bags 21 containing a diluent solution . Each bag 21 is connectable to a respective dispensing kit 6 in order to dilute the radiopharmaceutical in the relative tank 8 and / or f lush the dispensing kit 6 .

[0033] The radiopharmaceutical production system 1 comprises an active substance meter 22 having a measuring chamber 23 accessible from the work chamber 2 and adapted to contain the tank 8 of a dispensing kit 6 . The radiopharmaceutical production system 1 also comprises a load cell 24 connected to the measuring chamber 23 for measuring the weight of the content of the tank 8 when the latter is housed in the measuring chamber 23 .

[0034] The radiopharmaceutical production system 1 comprises an outlet port 25 for trans ferring the container 4 with a dose of radiopharmaceutical out of the work chamber 2 . In particular, the outlet port 25 is obtained in the f loor 11 . The outlet port 25 is provided with a lid 26 adapted to translate perpendicularly to the f loor 11 to close and open the outlet port 25 . Figure 1 shows the lid 26 raised and a container 4 inserted into the outlet port 25 . Advantageously, the outlet port 25 is provided with an actuator (not shown) for raising and lowering the lid 26 .

[0035] The radiopharmaceutical production system 1 comprises a manipulation system 27 for trans ferring the tank 8 of a certain dispensing kit 6 between the support 16 and the metering chamber 23 , for trans ferring the needle as sembly 9 of the dispensing kit 6 between the support 18 and the dispensing device 5 , for trans ferring an empty container 4 from the support 3 to the dispensing device 5 and for trans ferring a container 4 with the dose of radiopharmaceutical from the dispensing device 5 to the outlet port 25 .

[0036] The manipulation system 27 comprises at least one tele- plier, preferably manually control lable from outside of the work chamber 2 . In the example shown by Figure 1 , the manipulation system 27 comprises at least two tele-pliers preferably mounted on a front port of the insulator (not shown) , in particular a first tele-plier 28 for trans ferring the tank 8 of a certain dispensing kit 6 between the support 16 and the measuring chamber 23 and for trans ferring the needle assembly 9 of the dispensing kit 6 between the support 18 and the dispensing device 5 , and a second tele-plier 29 for trans ferring an empty container 4 from the support 3 to the dispensing device 5 and for trans ferring the container 4 with the dose of radiopharmaceutical from the dispensing device 5 to the outlet port 25 . The transfer towards and from the dispensing device 5 takes place by bringing and, respectively, withdrawing the container 4 in and, respectively, from the insertion position described above .

[0037] Each dispensing kit 6 comprises a plurality of conduits for connecting the tank 8 and the needle assembly 9 to each other and to various parts of the radiopharmaceutical production system 1 , as will be explained in detail below .

[0038] Figure 2 shows a dispensing kit 6 with the cassette 7 viewed from a front side 30 and Figure 3 shows the cassette 7 viewed from a rear side 31 which is open to be mounted on a control module 12 of the dispensing device 5 .

[0039] With reference to Figures 2 and 3 , the cassette 7 of the dispensing kit 6 comprises a control hydraulic circuit

[0040] 32 ( Figure 3 ) and the needle assembly 9 of the dispensing kit 6 comprises a needle 33 , which communicates with the control hydraulic circuit 32 and is insertable into the container 4 , a needle holder element 34 and a cap 35 couplable with the needle holder element 34 coaxially to a longitudinal axis 35a of the cap 35 to separate the needle

[0041] 33 from the external environment when the needle 33 is not used for dispensing . For example , when the needle assemblies 9 are stored in the support 18 , as shown in Figure 1 , they must have their respective caps 35 coupled with the relative needle holder elements 34 . Figure 2 , on the other hand, shows the cap 35 decoupled from the needle holder element 34 .

[0042] The needle holder element 34 is provided with a sealing element , for example O-ring 37 , for achieving a hermetic seal with the cap 35 . In particular, the needle holder element 34 comprises a neck 36 from which the needle 33 extends , the O-ring 37 is fitted on the neck 36 and the cap 35 is adapted to be fitted on the neck 36 at the O-ring 37 . The cap 35 compri ses a laterally proj ecting edge 38 to favour gripping of the cap 35 when it is desired to decouple it from the needle holder element 34 .

[0043] The plurality o f conduits of the dispensing kit 6 comprises a conduit 39 communicating with the bottom of the cap 35 and acting as a drain during a flushing of the dispensing kit 6 from radiopharmaceutical residues when the cap 35 is coupled to the needle holder element 34 . In use , the flushing of the dispensing kit 6 takes place at the end of the production of a batch of radiopharmaceutical , with the needle assembly 9 still on the support body 14 of the dispensing device 5 .

[0044] For this purpose , the conduit 39 of the cap 35 of each dispensing kit 7 ends with a connector 40 , which is connectable with a respective discharge conduit of a plurality of discharges 41 ( Figure 1 ) of the radiopharmaceutical production system 1 accessible from the work chamber 2 .

[0045] The needle assembly 9 comprises a second needle 42 communicating with the external environment through a ventilation hole 43 , which is obtained on the needle holder element 34 and is provided with a filter . The second needle 42 , which is shorter than the other needle 33 , allows air to escape from the container 4 when it is filled with the dose of radiopharmaceutical through the needle 33 .

[0046] Still with reference to Figure 2 , the dispensing kit 7 comprises a conduit 44 for connecting the needle 33 with the control hydraulic circuit 32 and the needle assembly 9 comprising a sterili zing filter 45 disposed between the conduit 44 and the needle 33 .

[0047] The plurality o f conduits of the dispensing kit 6 comprises a conduit 46 for filling the tank 8 with the radiopharmaceutical and two other conduits 47 and 48 for connecting the tank 8 with the control hydraulic circuit 32 . The conduits 46 , 47 and 48 extend into the tank 8 through a lid 49 of the tank 8 . The lid 49 has a ventilation hole 50 provided with a filter . The conduit 46 terminates with a connector 51 connectable with a respective delivery connector of a plurality of delivery connectors 52 ( Figure 1 ) of the radiopharmaceutical production system 1 accessible from the work chamber 2 for the supply of the undiluted radiopharmaceutical .

[0048] The plurality o f conduits of the dispensing kit 6 comprises a conduit 53 for connecting the control hydraulic circuit 32 with a bag 21 of diluent solution for the purpose of diluting the radiopharmaceutical in the tank 8 and / or flushing the dispensing kit 6 .

[0049] The plurality of conduits of the dispensing kit 6 comprises a conduit 54 for connecting the control hydraulic circuit 32 with a technical gas source (not shown) for the purpose of mixing the diluted radiopharmaceutical in the tank 8 or removing residues of radiopharmaceutical from the conduits during a flushing of the dispensing kit 6 .

[0050] The plurality o f conduits of the dispensing kit 6 comprises a conduit 55 closed on the control hydraulic circuit 32 and couplable with a peristaltic pump of the dispensing device 5, and in particular with the peristaltic pump 13 of the control module 12 on which the cassette 7 of the dispensing kit 6 is mounted .

[0051] With reference to Figure 3 , the control hydraulic circuit 32 comprises a plurality of three-way valves 56 , which communicate with each other and have respective control interfaces 57 facing the rear side 31 of the cassette 7 . In particular, each control interface 57 consists of a T-shaped control element adapted to move the internal shutter (not shown) of the respective three-way valve 56 .

[0052] With reference to Figures 1 to 3 and Figure 4 , the latter showing the uppermost control module 12 of the dispensing device 5 free from the respective cassette 7 , the front side 30 of each cassette 7 comprises a slot 58 engageable by a lever key 59 mounted on a front wall 60 of the control module 12 so as to rotate between a release position, wherein the lever key 59 is aligned with the slot 58 to allow mounting and dismounting of the cassette 7 from the control module 12 , such as for example the uppermost control module 12 shown in Figure 1 , and a locking position, wherein the lever key 59 is transverse to the slot 58 to lock the cassette 7 on the control module 12 , such as for example the three lowest control modules 12 of Figure 1 .

[0053] With reference to Figures 3 and 4 , each control module 12 comprises a plurality of rotatable actuators 61 comprising respective control elements 62 , each of which is couplable with a respective control interface 57 of the cassette 7 . In particular, each control element 62 consists of a pin suitably shaped to couple with the T-shape of the respective control interface 57 .

[0054] With reference to Figures 5 to 17 , which show the lower part of the dispensing device 5 comprising the support body 14 and the handl ing device 15 during subsequent operating steps of the dispensing device 5 concerning the handling and manipulation of the container 4 before and after a dispensing step of the dose of radiopharmaceutical , the support body 14 has a seat 63 for receiving the cap 35 . In particular, the seat 63 develops along a substantially vertical axis 63a and is adapted to receive the cap 35 coaxially, i . e . in the direction of the axis 63a . In this way, the entire needle assembly 9 is positionable on the support body 14 engaging the cap 35 in the seat 63 . The dispensing device 5 further comprises a retaining element 64 movably mounted on the support body 14 for retaining the cap 35 in the seat 63 and a clamp 65 designed to close around the needle holder element 34 when the cap 35 is in the seat 63 ( Figure 7 ) .

[0055] In particular, the retaining element 64 is movable between a release position, wherein it leaves the cap 35 free ( Figures 5 and 6 ) , and a retention position, wherein it is arranged above the edge 38 of the cap 35 to retain the latter in the seat 63 ( Figures 7 to 17 ) . In the example shown, the retaining element 64 has a first end hinged on the support body 14 to rotate around an axis parallel to the axis 63a of the seat 63 between the release position and the retention position and a second hook-shaped end 66 adapted to be arranged around the needle holder element 34 , and in particular the neck 36 , and overlap the entire edge 38 ( Figures 7 and 8 ) .

[0056] The dispensing device 5 comprises two actuators (not shown) for causing the rotation of the retaining element 64 and, respectively, the closing / opening of the clamp 65 .

[0057] When the clamp 65 is open and the retaining element 64 is in the release position ( Figure 5 ) , the needle assembly 9 is positionable on the support body 14 .

[0058] The dispensing device 5 comprises a handling device 67 to translate the support body 34 and the clamp 65 reciprocally with each other parallel to the axis 63a when the clamp 65 is closed on the needle holder element 34 and the retaining element 64 holds the cap 35 in the seat 63 so as to remove the cap 35 from the needle holder element 34 . In particular, the clamp 65 is mounted on the frame 10 and the handling device 67 is adapted to translate the support body 14 with respect to the frame 10 , and therefore with respect to the clamp 65 , downwards in the direction of the axis 63a ( Figure 8 ) .

[0059] The dispensing device 5 comprises a further actuator 68 for moving the clamp 65 , when it is closed, between a cap removal position, wherein the j aws of the clamp 65 are located above the seat 63 ( Figure 8 ) , and a dispensing position, wherein the aws of the clamp 65 are located further away from the seat 63 ( Figure 9 ) . In particular, the clamp 65 is mounted on the frame 10 to rotate , under the action of the actuator 68 , around an axis 65a parallel to the axis 63a .

[0060] The handling device 15 comprises a support body 69 and a conveyor 70 mounted on the support body 69 to define a path for the container 4 which extends between the insertion position, wherein the container 4 can be inserted or withdrawn into or from the dispensing device 5 ( Figure 9 ) , and the filling position, wherein the needle 33 enters the container 4 when the clamp 65 is in the dispensing position ( Figures 14 and 15 ) .

[0061] The conveyor 70 comprises a sliding plane 71 for the container 4 , a curved lateral sidewall 72 to define a U- shaped conveying path, and a rotating arm 73 , which is hinged on the support body 69 and has a U-shaped free end 74 to embrace and accompany the container along the sidewall 72 , and therefore along the conveying path . The conveyor 70 comprises an actuator 75 for causing the rotation of the rotating arm 73 . At the filling position, the sidewall 72 comprises a U-shaped end portion 76 for embracing the neck of the container 4 ( Figure 14 ) .

[0062] The dispensing device 5 comprises a ferrule removal / application device 77 and a plug removal / application device 78 which are arranged along the conveyor 70 at a first removal / application position ( Figure 10 ) and, respectively, a second removal / application position ( Figure 12 ) of the conveying path .

[0063] The dispensing device 5 further comprises a crimping device 79 arranged along the conveyor 70 at a crimping position of the conveying path ( Figure 16 ) , between the first removal / application position and the insertion position .

[0064] The conveyor 70 is adapted to bring and stop the container 4 in the aforementioned first and second removal / application positions and in the crimping position . The handling device 15 comprises an actuator 80 for raising the support body 69 , and therefore the conveyor 70 , when the container 4 is stopped in the first removal / application position or in the second removal / application position or in the filling position or in the crimping position to allow respectively : to the ferrule removal / application device 77 to remove / apply the ferrule 4a from / to the container 4 ( Figure 11 ) ; or to the plug removal / application device 78 to remove / apply the plug 4b from / to the container 4 ( Figure 13 ) ; or

[0065] - to the needle 33 to enter the container 4 when the clamp 65 is in the dispensing position ( Figure 15 ) ; or

[0066] - to the crimping device 79 to close the ferrule 4a on the container 4 containing the dose of radiopharmaceutical . The devices 77 , 78 and 79 described above operate in a substantially known manner . In particular, when the ferrule removal / application device 77 removes the ferrule 4a, it holds it for subsequent reapplication on the same container 4 and, similarly, when the plug removal / application device 78 removes the plug 4b, it holds it for subsequent reapplication on the same container 4 .

[0067] Finally, the radiopharmaceutical production system 1 comprises a control unit (not shown) having a human-machine interface . The control unit is adapted to control the actuators described above , and in particular the actuators of the dispensing device 5 , on the basis of commands that an operator gives through the human-machine interface in order to produce a plurality of batches of radiopharmaceutical , according to the following procedure .

[0068] The operator manually sets up the four dispensing kits 6 with the empty tanks 8 in the work chamber 2 and arranges a plurality of empty containers 4 provided with respective ferrules 4a and respective caps 4b on the support 3 , as shown in Figure 1 . At the end of the aforementioned set-up, the work chamber 2 is closed and the laminar flow is operated to maintain working conditions in class A.

[0069] The operator through the tele-plier 28 takes a tank 8 of a certain dispensing kit 6 from the support 16 and inserts it into the measuring chamber 23 . Then it activates the supply of the radiopharmaceutical to introduce a certain amount of radiopharmaceutical into the tank 8 , through the conduit 46 . The activity and the weight of the radiopharmaceutical in the tank 8 are measured and controlled by the active substance meter 22 and the load cell 24 .

[0070] In the event that it is necessary to dilute the radiopharmaceutical according to a certain medical prescription, the operator commands the control unit so that the control module 12 , and therefore the relative peristaltic pump 13 , associated with the dispensing kit 6 in use controls the cassette 7 to trans fer an amount of diluent solution from the relative bag 21 to the tank 8 , a trans fer that takes place through the conduit 53 and the conduits 47 and 48 . To mix the diluted radiopharmaceutical , the operator commands the control unit so that the control module 12 introduces the technical gas into the tank 8 , this introduction taking place through the conduit 51 and the conduits 47 and 48 .

[0071] The amount of radiopharmaceutical or diluted radiopharmaceutical in the tank 8 is that necessary to produce a batch of radiopharmaceutical . At this point , the dispensing of the radiopharmaceutical can be started in one container 4 at a time for all the containers necessary to produce the batch of radiopharmaceutical .

[0072] The operator commands the control unit so that the dispensing device 5 brings the retaining element 64 into the release position and opens the clamp 65 , and by means of the tele-plier 28 takes the needle assembly 9 of the di spensing kit 6 in use from the support 18 and brings it on the support body 14 inserting the cap 35 in the seat 63 ( Figure 5 ) . Then the operator commands the control unit so that the dispensing device 5 performs the following steps in sequence : close the clamp 65 ( Figure 6 ) , bring the retaining element 64 into the retention position ( Figure 7 ) , lower the support body 14 to remove the cap 35 from the needle holder element 34 ( Figure 8 ) and move the closed clamp 65 into the dispensing position ( Figure 9 ) .

[0073] The operator by means of the tele-plier 29 withdraws an empty container 4 from the support 3 and puts it in the insertion position, between the free end 74 and the sidewall 72 of the conveyor 70 (Figure 9) , and then commands the control unit so that the dispensing device 5 automatically performs a single dispensing cycle, i.e. on the container 4, described below.

[0074] The handling device 15 brings and stops the empty container 4 in sequence in the first removal / application position (Figures 10 and 11) , where the ferrule removal / application device 77 removes the ferrule 4a, in the second removal / application position (Figures 12 and 13) , where the plug removal / application device 78 removes the plug 4b, and finally in the filling position (Figures 14 and 15) .

[0075] At this point, the control module 12, and therefore the relative peristaltic pump 13, associated with the dispensing kit 6 in use commands the cassette 7 to transfer a dose of radiopharmaceutical from the tank 8 to the container 4, such transfer taking place through the conduit 44 and the conduit 47. The actual transfer of the dose of radiopharmaceutical is verified in a known manner through the peristaltic pump 13 and / or the active substance meter 22.

[0076] After filling the container 4 with the dose of radiopharmaceutical, the handling device 15 performs backwards some of the steps described above to put the plug 4b back to the container 4, thanks to the plug removal / application device 78 (Figures 13 and 12) , and reapply the ferrule 4a to the container 4, thanks to the ferrule removal / application device 77 (Figures 11 and 10) . However, before bringing the container 4 with the dose of radiopharmaceutical to the insertion position, the handling device 15 stops the container 4 in the crimping position where the crimping device 79 closes the ferrule 4a on the container 4 ( Figures 16 and 17 ) .

[0077] The handling device 15 closes the single dispensing cycle by returning the container 4 closed with the dose of radiopharmaceutical to the insertion position ( Figure 9 ) .

[0078] The operator commands the control unit to open the lid 26 of the outlet port 25 ( Figure 1 ) and by means of the tele- plier 29 withdraws the full container 4 from the di spensing device 5 and trans fers it to the outlet port 25.

[0079] The operator repeats the single dispensing cycle , each time withdrawing an empty container 4 from the support 3 via the tele-plier 29, leaving the clamp 65 with the needle 33 in the dispensing position, until the entire batch of radiopharmaceutical is produced .

[0080] Once the production of the batch o f radiopharmaceutical is ended, the operator commands the control unit so that the dispensing device 5 returns the closed clamp 65 to the cap removal position ( Figure 8 ) , li fts the support body 14 to put the cap 35 back on the needle holder element 34 ( Figure 7 ) and, by appropriately controlling the control module 12 associated with the dispensing kit 6 in use , performs a flushing cycle of the dispensing kit 6 itsel f using the diluent solution of the relative bag 21 . The flushing cycle allows residues of radiopharmaceutical to be removed from the dispensing kit 6 and be discharged, through the conduit 39 of the cap 35 and the relative discharge conduit 41 ( Figure 1 ) , into a special container outside the pharmaceutical isolator .

[0081] At the end of the flushing cycle , the operator commands the control unit so that the dispensing device 5 brings the retaining element 64 into the release position ( Figure 6 ) and opens the clamp 65 ( Figure 5 ) . Then, by means of the tele-plier 28 , the operator takes from the support body 14 the needle assembly 9 of the dispensing kit 6 j ust flushed and puts it back in the respective seat of the support 18 and takes the tank 8 from the measuring chamber 23 and puts it back in the respective seat of the support 16 .

[0082] At this point , without having to open the work chamber 2 to withdraw the dispensing kit 6 j ust used and flushed, the operator can repeat the procedure described above by selecting another dispensing kit 6 to produce a subsequent batch of radiopharmaceutical . Therefore , the dispensing kit 6 j ust used is left in the work chamber 2 as initially set up and will be collected and disposed of only together with the other dispens ing kits 6 at the end of the production of all the batches of radiopharmaceutical .

[0083] Although the invention described above makes particular reference to a very precise example of embodiment , it is not to be considered limited to this example of embodiment , falling within its scope all those variants , modi fications or simpli fications covered by the appended claims , such as , for example :

[0084] - the manipulation system 27 comprises a single tele- plier ; instead of the tele-pliers , a fully automatic manipulation system; and

[0085] - the dispensing device 5 comprises a single control module 12 and the radiopharmaceutical production system 1 comprises a further support for supporting the cassettes 7 of the dispensing kits 6 , so that each time the dispensing kit 6 in use is changed, the operator must mount the cassette 7 on the control module 12 with the aid of the tele-pliers 28 and 29 .

[0086] The main advantage of the dispensing kit 6 , of the dispensing device 5 and of the radiopharmaceutical production system 1 described above is to allow the production of a plurality of batches of radiopharmaceutical avoiding cross-contamination between di f ferent batches without the need to have to clean the work chamber 2 from the residues of contaminating substances , i . e . residues of radiopharmaceutical , between successive batches , thanks to the cap 35 protecting the needle 33 used for dispensing and to the mechanisms of the dispensing device 5 to remove and put the cap 35 back when the needle 33 is not used for dispensing, which allow to reduce the exposure to the environment of the surfaces in contact with the radiopharmaceutical .

[0087] Furthermore , the conduit 39 of the cap 35 and the discharge conduits 41 that open into the work chamber 2 and that are connectable to the conduits 39 of the dispensing kits 6 set up in the work chamber 2 , allow to eliminate the residues of contaminating substances inside the dispensing kits 6 , and therefore further reduce the risk of crosscontamination in the work chamber 2 and allow to collect the residues of contaminating substances in appropriate external disposal containers .

[0088] Consequently, since it is not necessary to open and clean the work chamber 2 after each batch of radiopharmaceutical , the daily production capacity will be increased .

Claims

CLAIMS1. A dispensing kit for a dispensing device to dispense a radiopharmaceutical in at least one container, particularly vials, bottles, flasks, or syringes, the dispensing kit (6) comprising: a cassette (7) , which encloses a control hydraulic circuit (32) and is mountable on the dispensing device (5) ; a tank (8) for a bulk radiopharmaceutical, communicating with the control hydraulic circuit (32) ; a needle assembly (9) , which comprises a needle (33) communicating with the control hydraulic circuit (32) and insertable into the container (4) to introduce a dose of radiopharmaceutical into it, a needle holder element (34) and a cap (35) couplable with the needle holder element (34) , preferably by the interposition of a sealing element (36) , to separate the needle (33) from the external environment when the needle (33) is not used for dispensing; and a plurality of conduits comprising a first conduit (39) communicating with the bottom of the cap (35) and acting as a drain to flush the dispensing kit (6) of radiopharmaceutical residues when the cap (35) is coupled to the needle holder element (34) .

2. The dispensing kit according to claim 1, wherein the plurality of conduits includes a second conduit (46) for filling the tank (8) with the radiopharmaceutical and a third conduit (47) and a fourth conduit (48) for connecting the tank (8) with the control hydraulic circuit (32) .

3. The dispensing kit according to claim 1 or 2, wherein the plurality of conduits includes a fifth conduit (53) for connecting the control hydraulic circuit (32) with a bag (21) of diluent solution for the purpose of diluting the radiopharmaceutical in the tank (8) and / or flushing thedispensing kit (6) .

4. The dispensing kit according to any one of claims 1 to 3, wherein the plurality of conduits includes a sixth conduit (54) for connecting the control hydraulic circuit (32) with a technical gas source for the purpose of mixing radiopharmaceutical in the tank (8) or removing residues of radiopharmaceutical from the conduits during a flushing of the dispensing kit (6) .

5. The dispensing kit according to any one of claims 1 to 4, wherein the plurality of conduits comprises a seventh conduit (44) for connecting the needle (33) with the control hydraulic circuit (32) ; the needle assembly (9) comprising a sterilizing filter (45) disposed between the seventh conduit (44) and the needle (33) .

6. The dispensing kit according to any one of claims 1 to 5, wherein the plurality of conduits comprises an eighth conduit (55) closed on the control hydraulic circuit (32) and couplable with a peristaltic pump (33) of the dispensing device (5) .

7. The dispensing kit according to any one of claims 1 to 6, wherein the control hydraulic circuit (32) comprises a plurality of three-way valves (56) , which communicate with each other and have respective control interfaces (57) facing an open side (31) of the cassette (7) ; the cassette (7) being mountable on the dispensing device (5) from said open side (31) .

8. A dispensing device for dispensing a radiopharmaceutical in at least one container, in particular a vial, bottle, flask or syringe, cooperating with at least one dispensing kit (6) according to any one of claims 1 to 7, the dispensing device (5) comprising: a frame (10) ; atleast one control module (12) , which is integral with the frame (10) and on which the cassette (7) is releasably mountable; a support body (14) presenting a seat (63) for receiving said cap (35) ; a retaining element (64) movably mounted on the support body (14) for retaining the cap (35) in the seat (63) ; a clamp (65) designed to close around said needle holder element (34) when the cap (35) is in the seat (63) ; a first handling device (67) to translate the support body (14) and the clamp (65) reciprocally with each other when the clamp (65) is closed on the needle holder element (34) and the retaining element (64) holds the cap (35) , so as to remove the cap (35) from the needle holder element (34) ; an actuator (68) to move the clamp (65) between a cap removal position and a dispensing position; and a second handling device (15) to move the container (4) between an insertion position, wherein the container (4) can be inserted or withdrawn into or from the dispensing device (5) , and a filling position, wherein the needle (33) enters the container (4) when the clamp (65) is in the dispensing position .

9. The dispensing device according to claim 8, wherein the dispensing kit (6) is according to claim 6 and said control module (12) comprises a peristaltic pump (13) .

10. The dispensing device according to claim 8 or 9, wherein the dispensing kit (6) is according to claim 7 and said control module (12) comprises a plurality of actuators (61) comprising respective control elements (62) couplable with respective of said control interfaces (57) of the cassette ( 7 ) .

11. The dispensing device according to any one of claims 8 to 10, wherein the seat (63) develops along a first axis(63a) and is designed to receive the cap (35) coaxially, and the clamp (65) is mounted on the frame (10) to rotate, under the action of the actuator (68) , about a second axis (65a) parallel to the first axis (63a) .

12. The dispensing device according to claim 11, wherein the first handling device (67) is configured to translate the support body (14) relative to the frame (10) in the direction of the first axis (63a) .

13. A radiopharmaceutical production system to produce a plurality of batches of radiopharmaceuticals, each of which consists of a set of radiopharmaceutical doses contained in respective containers (4) , particularly vials, bottles, flasks or syringes, the radiopharmaceutical production system (1) comprising: an isolator, which is shielded against ionizing radiation and has a work chamber (2) ; a dispensing device (5) arranged in the work chamber (2) ; a plurality of dispensing kits (6) , each of which is according to any one of claims 1 to 7, is associated with a respective batch of radiopharmaceutical, and is set up in the work chamber (2) so as to cooperate with the dispensing device (5) to introduce radiopharmaceutical doses into respective containers (4) ; a first support (16) arranged in the work chamber (2) for receiving the tanks (8) of the dispensing kits (6) ; a second support (18) arranged in the work chamber (2) for receiving the needle assemblies (9) of the dispensing kits (6) ; a plurality of discharge conduits (41) , each of which is accessible from the work chamber (2) and is connectable to the first conduit (39) of a respective dispensing kit (6) ; a third support (3) arrangeable in the work chamber (2) for arranging in an orderly manner empty containers (4) ; and a handling system (27) , preferablycomprising at least one tele-plier (28, 29) , to transfer the needle assembly (9) of a certain dispensing kit (6) between the second holder (18) and the dispensing device (5) and to transfer an empty container (4) from the third holder (3) to the dispensing device (5) .

14. The radiopharmaceutical production system according to claim 13, wherein said dispensing device (5) is according to any one of claims 8 to 12 and preferably comprises a plurality of control modules (12) , on each of which the cassette (7) of a respective dispensing kit (6) is releasably mountable .

15. The radiopharmaceutical production system according to claim 13 or 14, and comprising an active substance meter (22) having a measuring chamber (23) accessible from the work chamber (2) and adapted to contain the tank (8) of said certain dispensing kit (6) ; the handling system (27) being adapted to transfer the loading reservoir (8) of said certain dispensing kit (6) between the first holder (16) and the measuring chamber (23) .

16. The radiopharmaceutical production system according to any one of claims 13 to 15, wherein the work chamber (2) comprises an outlet port (25) for transferring a container (4) containing a dose of radiopharmaceutical out of the work chamber (2) , and said manipulation system (27) being adapted to transfer the container (4) containing a dose of radiopharmaceutical from the dispensing device (5) to the outlet port (25) .

17. The radiopharmaceutical production system according to any one of claims 13 to 16, wherein the manipulation system (27) comprises at least a first tele-plier (28) for transferring the needle assembly (9) of said certaindispensing kit (6) between the second holder (18) and the dispensing device (5) , and a second tele-plier (65) to transfer the empty container (4) from the third holder (3) to the dispensing device (5) and the container (4) containing a dose of radiopharmaceutical from the dispensing device (5) to the outlet port (25) .

18. The radiopharmaceutical production system according to any one of claims 13 to 17, wherein each dispensing kit (6) is according to claim 3 and the radiopharmaceutical production system (1) comprises a fourth holder (20) for supporting a plurality of bags (21) of diluent solution, each of which is connectable to the fifth port (53) of a respective dispensing kit (6) .

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