Patent Application
20240025578
The present invention relates to a device and method for assembling and filling containers for a needle-free injection device with sterile pharmaceutical products.
More precisely, the device and method of the invention relate to automated, industrial assembly and filling of a container such as a tube with a sterile solution.
Traditionally, the vast majority of medicines were packaged in vials (glass or sometimes plastic bottles). In certain cases, the vials contained medicines in solution, whereas in others, they were solid and had to be reconstituted using a solution to make an injectable drug solution. In the latter case, medicines were administered to the patient after being reconstituted by a physician or pharmacist in a glass syringe; this method involved, on the one hand, a risk of dosing error in terms of both reconstitution and injectable dose, and on the other hand, a risk of contaminating the sterile solution. To reduce this risk, for decades manufacturers have started to package their product in pre-filled, ready-to-use delivery devices. These delivery devices typically contain a single dose. The other advantage of pre-filled devices is that they save on the active ingredient, which is used in smaller quantities.
Nowadays, most pre-filled delivery devices are provided with a glass or plastic tube which contains the drug solution, such as pre-filled syringes.
The ISO 11040 standard defines pre-filled syringes. It describes pre-fillable, pre-assembled syringes as well as piston stoppers and rods. This applies to both glass and plastic syringes. A pre-filled syringe is a container filled with injectable product, ready for injection. The syringe barrel is a cylindrical glass barrel equipped with one end onto which the needle is attached and a flange. A pre-fillable sterilised pre-assembled syringe is a sub-assembly where each component has undergone pre-treatment, composed of a syringe barrel and a closure system at the end onto which the needle is attached. The sub-assembly must have been pre-treated by applying at least one of the following steps: assembling/lubricating a needle, final washing/pyrogen reduction, drying, applying a lubricant to the inner surface, sealing the syringe with a closure system, packaging and sterilising. In other words, the pre-fillable sterilised pre-assembled syringe comprises the cylindrical barrel but the flange surrounding the orifice opposite the syringe barrel relative to the end provided with the closure system is free. This orifice will later be used to fill the syringe and will then receive the piston stopper, commonly called the piston seal, as well as the rod.
In the case of pre-fillable sterilised pre-assembled syringes, responsibility for the above-mentioned steps relating to the injectable product lies with the primary packaging manufacturer.
After assembling the needle cover on the syringes, the pre-assembled syringes are placed in what are known as nests. A nest is a holder, often made of plastic, equipped with holes for receiving syringes or other containers provided with an upper opening. The nests are then placed into plastic trays called tubs. The syringes placed in the nest are protected by a separator film and the tub is sealed with a sealing cap. The assembly is then double or triple packed to ensure a sterile barrier system. This makes it possible to deliver pre-fillable sterilised pre-assembled syringes to pharmaceutical companies for subsequent filling, or to subcontracting companies for the same filling purposes.
The growing global prevalence of chronic, lifestyle-related illnesses is also increasing demand for pre-filled delivery technology. In the case of regular, even daily treatment, it is important to develop treatments that may be administered simply and/or painlessly by the patient themselves, directly at home. The advantage of pre-filled devices is that they remove the step of preparing the medicine and thereby remove the risk of contamination associated with this preparation.
However, many disadvantages remain, such as the disposal of syringes and needles, the occurrence of broken needles, the “fear of needles” and the risk of infection at the injection site.
In recent years, a great deal of research has been carried out into needle-free or microneedle transdermal injection devices.
These needle-free injection devices inject the drug substance under the skin using a jet or under high pressure. The sterile containers used in these needle-free transdermal injectors are generally tubes capped on both sides with removable caps. For example, the company Crossject and its pre-filled, single-use Zeneo® needle-free injection device, which propels the solution through the skin (subcutaneous) or through the muscles (intramuscular) in less than a tenth of a second.
The market for pre-filled delivery devices is continuing to expand, driven both by the growing needs of patients and by the pharmaceutical industry's drive to reduce costs and increase efficiency. In recent years, wearable devices have become increasingly popular, which has also increased demand for pre-filled devices.
Automatic aseptic filling machines for syringe barrels are well known from prior art. Glassmakers manufacture and supply glass tubes with an opening for receiving a liquid. The tubes or syringe barrels are arranged on a nest, i.e. a plastic holder with holes for receiving tubes. The holders are then arranged in tubs, i.e. transport containers, which are sealed with a film of synthetic material, which is in turn packaged in one or more bags of synthetic material. The containers are sterilised, sent, and then received by the pharmaceutical company or subcontractor who unpacks the tubs in an aseptic environment. The nests are then removed from their tubs and either the containers or the nests are then placed in a loading area to supply containers to an automatic lengthwise filling machine. The loading area is located upstream of the filling area. In the filling area, the syringe tube, sealed at the bottom, is filled through the upper orifice from the bottom of the tube by a stroke-adjustable descending-ascending injector.
Once the tube is filled, it is then capped in a capping area, generally by introducing the piston cap downstream of the filling area. All of the loading, supplying, filling and capping areas follow each other in a linear machine. The disadvantage of these machines is that they require large, expensive infrastructures to install all the parts of the linear chain to obtain the filled tubes.
The terms “capped” and “plugged” or “capping” and “plugging” or even “grade(s)” and “class(es)” or “vibrating” and “vibratory” are used interchangeably in the present patent application.
Document EP3074313 discloses a sterile packaging facility for dermo-cosmetic or galenic preparations, wherein the preparation is placed into a cone-shaped or inverted pyramid-shaped discharge hopper which acts as a funnel to fill the container. The container is brought under the hopper by a transfer device. The whole facility is located in a sterile enclosure with a device for blowing ultra-filtered air from the ceiling to the floor of the enclosure to produce an anti-particle air flow around the filling area.
Document EP3493783 discloses an aseptic distribution line for pharmaceutical products, such as solutions to be packaged in pre-filled injectable syringes. Distribution is carried out in a grade A sterile area contained in an isolator. The grade A area is surrounded by a grade C area in which the operators who are needed to operate the line work. The isolator is provided with three systems for generating hydrogen peroxide vapour to decontaminate the surfaces within the isolator. The laminar flow isolator maintains a grade A sterile environment. Fluidised air is used for air treatment to protect critical areas by controlling the risks of particulate and microbiological contamination and cross-contamination. The air is filtered by absolute filters and a pressure cascade is maintained. The isolator is provided with glove boxes to allow grade A handling by authorised personnel when operating the machine or carrying out unscheduled maintenance. The syringes used are received ready for use, i.e. provided in sterile packaging inside sealed tubs. The tubs are introduced into the isolator via a conveyor and are surface sterilised using ionising radiation in order to be introduced into the grade A area. Once this step is complete, the tubs are opened using heat lamps and rollers with suction cups. After this step, the syringes are directly exposed to the grade A environment of the isolator. The distribution machine is supplied with solution by a direct pipe, which has been cleaned and sterilised in-situ. This solution is then filtered before being distributed into the syringes. After the filling station, the filled syringes then arrive at the capping station where a piston seal is inserted into the syringe barrel. This system ensures that the components remain sterile after sterilisation by autoclaving.
Unfortunately, with such devices, sources of contamination from airflow, handling, packaging or materials may be present in the filling area. Another disadvantage of these devices is the filling costs associated with the size of the facilities and the personnel required to operate them.
All these methods can be used to fill a container with a closed end, such as in syringes or vials. These methods are therefore not applicable to through tubes.
Yet given the growing demand for needle-free transdermal injectors, there is therefore a need to provide a method for filling through tubes in the pharmaceutical field, while maintaining the sterility of the components. Unfortunately, at this stage, although needle-free medical devices are on the rise, current demand is for medium-sized batches and it is difficult to envisage developing very long, very expensive facilities requiring a lot of investment to implement a filling method for a single type of container.
The object of the invention is to provide a method for assembling and filling containers which may be implemented with a compact, less expensive facility and which limits the risks of particulate and microbiological contamination.
To solve this problem, the invention provides a method for assembling and filling z containers for needle-free injection devices, each container comprising:
For the purposes of the present invention, the term “sterile” means a treatment that results in the maximum universal probability of a Non Sterile Unit (PNSU) per 106 units.
For the purposes of the present invention, the term “grade A” means grade A as defined in Annex 1 of the 2008 Eudralex document, The Rules Governing Medicinal Products in the European Union, Volume 4, EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use; grade A is defined on page 2 and page 3 (table).
For the purposes of the present invention, the term “grade B” means grade B as defined in Annex 1 of the 2008 Eudralex document, The Rules Governing Medicinal Products in the European Union, Volume 4, EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use; grade B is defined on page 3.
For the purposes of the present invention, the term “grades C and D” means grades C and D as defined in Annex 1 of the 2008 Eudralex document, The Rules Governing Medicinal Products in the European Union, Volume 4, EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use; grades C and D are defined on page 3.
For the purposes of the present invention, the term “sterile formulation for pharmaceutical use” means any sterile substance used for its curative or preventative properties with regard to diseases or symptoms, administered to the human or animal body. For the purposes of the present invention, the term “pharmaceutical” therefore covers all substances for both human and veterinary use.
As can be seen, according to the present invention, the method comprises a step of placing lower caps during which at least one lower cap is introduced at least partially into said lower orifice of a tube of said series of tubes to form at least one lower-sealed tube. Next, once sealed at the lower end, the tube is then filled by discharging a sterile formulation to be injected before sealing the upper orifice of the lower-sealed and filled through tube with an upper cap. In this manner, it is possible to aseptically fill any type of container with an opening on either side of the container barrel while the sterility of the formulation being discharged is maintained during the critical steps.
For the purposes of the present invention, the term “critical step” means a step where the formulation is exposed to open air.
According to the present invention, contrary to syringe filling lines where all actions are carried out from top to bottom, i.e. discharging the pharmaceutical solution into the syringe and then introducing the piston cap through the same upper orifice, it has been made possible to act on the through tube both from the top and from the bottom of the tube. According to the present invention, the lower cap is introduced through the lower orifice whereas the filling and placement of the upper cap are done through the upper orifice.
The introduction of the lower cap through the lower orifice, which must be correctly orientated and supplied at the same time as the tube is supplied to the lower capping area, is all the more surprising given that one of the main constraints is to remain within a small space.
As can be seen, the lower cap is introduced at least partially into the lower orifice of the tube, allowing the cap to be positioned correctly and reproducibly from one tube to the next. If the lower cap were introduced through the top and therefore through the upper orifice of the tube, the positioning of the lower cap would thus be random or, in any case, might not be perfectly positioned, since the cap would have to pass through the entire height of the tube to be positioned on the lower portion of the tube. The elasticity of the cap makes it difficult to place within the tube, particularly in a glass tube into which the cap is forced to ensure it is sealed. Moreover, the elastic material of the cap is coated with silicone, which would be randomly and non-reproducibly deposited in the tube as it passes through. There is significant friction when an elastic material is passed through a glass tube with a narrow diameter. As a result, introducing a cap through the top of the tube to reach the bottom end thereof could result in partial compression of portions of the cap, which could then result in a cap that is tilted or even turned around in the tube, unevenly distributed and/or partially compressed and a silicone deposit in the tube. This random positioning of the lower cap when introducing it through the top would therefore have an impact on the amount of sterile formulation to be injected and on the positioning of the upper cap (height, horizontality) and even on the seal of the cap.
According to the present invention, the various steps of the filling method are carried out as the carousel rotates. The rotating carousel comprises a plate provided with housings, each provided with a through orifice and an upper wall. The housing of the carousel receives the tube. The tube rests on the upper wall of the carousel via the upper flange thereof which is wider than the tubular wall of the tube or via the lower flange thereof, which is also wider than the tubular wall of the tube, as appropriate. Positioning the tube in an orifice of a carousel housing means that the tube can still be accessed via the lower orifice and/or the upper orifice, which is not the case in the prior art, where the tube can only be accessed via the upper orifice.
According to the present invention, introducing the bottom cap through the lower orifice of the tube is made possible both by the orifice of the carousel housing and by the rotation the carousel allowing the tube to be moved into the various action areas. The combination of the rotating carousel and the fact that each carousel housing has an orifice means that actions can be carried out via the top and bottom of the tube while leaving the lower and upper orifices of the tube accessible. Thanks to the carousel, the filling and capping steps are carried out sequentially by moving the tube along a rotating movement trajectory of the carousel. The tube positioned in a housing moves along a circular trajectory and not along a linear trajectory, which allows the robotic arms acting to carry out the various method steps according to the present invention to be offset from one another, thus allowing them to be suitably mobile without the risk of collisions between robotic arms and more flexible in terms of the movements that the robotic arm can perform. Moreover, the rotating carousel is suitable for smaller-sized pharmaceutical facilities and takes up less space by giving access to the tubes via the top and via the bottom, contrary to existing linear filling lines for pre-filled syringes where the syringe barrels are only accessible via the top.
According to the present invention, the sealed and filled tube is then placed onto a nozzle. The nozzle, with the tube, forms an assembled and filled container that is ready to be inserted into a needle-free injection device. The nozzle therefore enables the tube to be adjusted within the needle-free injection device.
According to the present invention, supplying a series of tubes is carried out according to the steps of:
Alternatively, the method according to the present invention may also comprise washing, depyrogenation and/or sterilisation steps if the nest tubes are not ready to use.
In an advantageous embodiment according to the invention, the areas selected from the supplying area, the lower capping area, the filling area, the upper capping area and the collecting area, are occupied by a housing of the series of housings of the carousel, so that rotating the carousel allows the housings of the series of housings to move from one area to another.
Preferably, according to the invention, the number of housings of the series of housings is equal to or greater than 2, preferably equal to or greater than 3, preferably equal to or greater than 4, preferably equal to or greater than 5 corresponding to the minimum number of areas.
Advantageously, the number of housings of the series of housings is greater than 5 and wherein a housing of the series of housings is positioned between two areas selected from the supplying area, the lower capping area, the filling area, the upper capping area and the collecting area, provided with or without a tube.
In an advantageous embodiment according to the invention, each sealed and filled tube positioned in the collecting area is grabbed by a third robotic arm, provided with gripping means, and is conveyed by the third robotic arm into a tray comprising a series of positions occupied by nozzles at the predetermined position of the tube on the nozzle to which it is assembled to form an assembled and filled container for needle-free injection devices.
Advantageously, according to the invention, the tray comprising assembled and filled containers for needle-free injection devices is placed into a tub by a moving means, for example, by a fourth robotic arm or a conveyor.
Preferably, according to the invention, each sealed and filled tube is then positioned in a nozzle placement area where a nozzle is connected to the sealed and filled tube by supplying a nozzle with a nozzle means provided with a head moving from the bottom upwards and the head of which, provided with the nozzle in the bottom position, moves vertically upwards to place the nozzle when the head is in the top position and form the assembled and filled container for needle-free injection devices, and returns to its bottom position without the nozzle, the nozzle means being positioned under the carousel.
The invention also relates to the lower capping carried out in the lower capping area by supplying a lower cap using a first piston provided with a piston head moving from the bottom upwards and the piston head of which, provided with the cap in the bottom position, moves vertically upwards into the lower orifice of the housing of the tube to place the lower cap therein when the head is in the top position and form said lower-sealed tube, and returns to its bottom position without the lower cap, said first piston being positioned under the carousel.
Preferably, the method according to the invention comprises a step of injecting inert gas before and/or during and/or after the lower capping step to remove oxygen. The inert gas is selected from nitrogen, argon and/or the like. Injecting inert gas prevents any degradation of the solution to be injected, reduces the effect of oxidation and preserves the effectiveness of this solution. Another advantage is that the through tube further allows more efficient purging of an inert gas. Particularly advantageously, a gas source is directly connected to a clamp to grip the tube as well as inject gas into any carousel area, for example, using a double-casing clamp.
In an advantageous embodiment according to the invention, the filling of the at least one lower-sealed tube is carried out by discharging sterile formulation to be injected into the at least one lower-sealed tube using a filling needle arranged to discharge a predetermined amount at a flow rate such that the predetermined amount is discharged during a residence time T which is shorter than or equal to the residence time of the lower-sealed tube in the filling area, to form the at least one lower-sealed and filled tube, the filling needle being positioned above the carousel.
Preferably, the method according to the invention comprises a step of injecting gas before and/or during and/or after the filling step to remove oxygen and/or activate the solution. If the gas is an inert gas, it is selected from nitrogen, argon and/or the like. If the gas is not an inert gas, for example for activating the solution, carbon dioxide may be included. Particularly advantageously, an inert gas source is directly connected to the filling needle to inject gas into any carousel area, for example using a double-channel filling needle, in particular with concentric double channels.
Advantageously, according to the invention, the filling needle is slidable and has a top resting position and a bottom filling position, the fluid movement forming a filling curve.
Preferably, the method according to the invention comprises a step of checking the filling volume of each lower-sealed and filled tube using means for measuring the filling volume, comprising a calibration unit and a high-precision measurement unit.
In an advantageous embodiment of the method according to the invention, the upper capping is carried out in the upper capping area by supplying an upper cap using a second piston provided with a piston head moving from the top downwards and the piston head of which, provided with the upper cap in the top position, moves vertically downwards into the upper orifice of the lower-sealed and filled tube to place the upper cap therein when the head is in the bottom position and form the sealed and filled tube, and returns to its top position without the upper cap, said second piston being positioned above the carousel.
Preferably, the method according to the present invention comprises a step of injecting inert gas before and/or during and/or after the upper capping step to remove oxygen and protect the solution by expelling carbon dioxide. The inert gas is selected from nitrogen, argon and/or the like. Injecting inert gas prevents any degradation of the solution to be injected, reduces the effect of oxidation and preserves the effectiveness of this solution.
Advantageously, the method comprises, after the upper capping step, a step of checking the space created between the solution and the upper cap by measuring the height between the top of the meniscus of the solution and the lower end of the upper cap. In practice, this checking step comprises checking the position of the upper cap using a camera. The height between the top of the meniscus of the solution and the lower end of the upper cap is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0.35 mm. Particularly advantageously, a gas source is directly connected to a clamp to grip the tube as well as inject gas into any carousel area, for example, using a double-casing clamp.
In an advantageous embodiment, the steps are carried out consecutively by continuously moving the plate of the carousel.
In an advantageous embodiment, the steps are carried out consecutively by discontinuously moving the plate of the carousel.
The invention also relates to a device for assembling and filling z containers for needle-free injection devices, each container comprising:
Advantageously, according to the invention, the supply means for a series of upper caps is located in an upper capping area and comprises a vibrating bowl arranged to contain a series of upper caps and position them in an insertion position, a second piston provided with a piston head arranged to move from the top downwards and introduce the at least one upper cap into the upper orifice of the at least one tube of the series of tubes and a conveyor connected to the vibrating bowl and to the second piston, the conveyor being arranged to supply the at least one upper cap in the insertion position to the piston head of the second piston.
In an advantageous embodiment according to the invention, the supply means for a series of lower caps are located in a lower capping area and comprise a vibrating bowl arranged to contain a series of lower caps and position them in an insertion position, a first piston provided with a piston head arranged to move from the bottom upwards and introduce the at least one lower cap into the lower orifice of the at least one tube of the series of tubes and a conveyor connected to the vibrating bowl and to the first piston, the conveyor being arranged to supply the at least one lower cap in the insertion position to the piston head of the first piston.
Advantageously, according to the invention, the filling means for the at least one lower-sealed tube comprises a sterile injectable solution tank and a filling needle connected to the sterile injectable solution tank by a supply duct, the needle being arranged to discharge a predetermined amount at a flow rate such that the predetermined amount is discharged during a residence time T which is shorter than or equal to the residence time of the lower-sealed tube in the filling area, the filling needle being positioned above the plate of the carousel.
In an advantageous embodiment of the device according to the invention, the supply means for a series of z tubes arranged to supply at least one tube of the series of z tubes into at least one housing of the carousel comprises:
Advantageously, according to the invention, the filling needle is slidable and has a top resting position and a bottom filling position, the fluid movement forming a filling curve.
Preferably, according to the invention, the supply means for at least one nozzle arranged to supply a nozzle to be connected to the at least one sealed and filled tube comprises a third robotic arm provided with a clamp, arranged to pick up each sealed and filled tube positioned in the collecting area and convey it into a tub comprising a series of positions occupied by nozzles at the predetermined position of the tube on the nozzle to be assembled to form an assembled and filled container for needle-free injection devices.
In an advantageous embodiment of the invention, the supply means for at least one nozzle arranged to supply a nozzle to be connected to the at least one sealed and filled tube comprises supply means for at least one nozzle by a nozzle means provided with a head moving from the bottom upwards and the head of which, provided with the nozzle in the bottom position, moves vertically upwards to place the nozzle when the head is in the top position and form the assembled and filled container for needle-free injection devices in a nozzle placement area of the carousel, and returns to its bottom position without the nozzle, the nozzle means being positioned under the carousel and where the collecting means comprise a third robotic arm provided with a clamp, arranged to pick up an assembled and filled container and convey it into a tray.
Preferably, the device according to the invention comprises means for measuring the filling volume of each lower-sealed and filled tube comprising a calibration unit and a high-precision measurement unit.
Preferably, the lower capping area further comprises an area for injecting inert gas to remove oxygen. The inert gas is selected from nitrogen, argon and/or the like. Injecting inert gas prevents any degradation of the solution to be injected, reduces the effect of oxidation and preserves the effectiveness of this solution. Another advantage is that the through tube further allows more efficient purging of an inert gas.
Preferably, the filling further comprises an area for injecting gas to remove oxygen and/or activate the solution. If the gas is an inert gas, it is selected from nitrogen, argon and/or the like. If the gas is not an inert gas, for example for activating the solution, carbon dioxide may be included. Particularly advantageously, an inert gas source is directly connected to the filling needle to inject gas into any carousel area, for example using a double-channel filling needle, in particular with concentric double channels.
Preferably, the upper capping area further comprises an area for injecting inert gas to remove oxygen and protect the solution by expelling carbon dioxide. The inert gas is selected from nitrogen, argon and/or the like. Injecting inert gas prevents any degradation of the solution to be injected, reduces the effect of oxidation and preserves the effectiveness of this solution.
Advantageously, the upper capping area is coupled with an area for checking the space created between the solution and the upper cap by measuring the height between the top of the meniscus of the solution and the lower end of the upper cap. This checking area further comprises means for checking the position of the upper cap; preferably, the checking means is a camera. The height between the top of the meniscus of the solution and the lower end of the upper cap is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0.35 mm.
Other embodiments of the device according to the invention and other embodiments of the method are mentioned in the appended claims.
Other features, details and advantages of the invention will emerge from the description given below, which is non-limiting and refers to the drawings and examples.
In the figures, the same or analogous items bear the same references.
The list of references used is described below:
Other features and advantages of the present invention will emerge from the following description, which is non-limiting, and with reference to the drawings.
As mentioned above, the present invention relates to the field of needle-free transdermal injection devices that give excellent results in terms of rapid and even distribution in the human or animal body, without really requiring expertise or posing any risk of poorly localised injection.
These needle-free injection devices inject the contained drug substance under the skin by a jet or under high pressure. The drug substance is contained in a sterile container. The sterile container is introduced into a needle-free transdermal injector.
The nest 29 is a holder, often made of plastic, equipped with tube receiving holes 30. The nest is placed into a tub 28 sealed by a sealing cap 44 to obtain a sterile barrier system.
Each tube 1 comprises a tubular wall 2, an upper orifice 3, a lower orifice 4, an upper flange 5 extending peripherally from the tubular wall 2 around the upper orifice 3 and a lower flange 6 extending peripherally from the tubular wall 2 around the lower orifice 4.
As can be seen in
The device according to the present invention also comprises a supply means 11, 13 for a series of lower caps 8. The supply means 11, 13 is located under the plate 23 of the carousel and is arranged to supply a lower cap 8 at least partially into the lower orifice 4 of the tube 1 in the housing 24 of the carousel 22 in position C to form at least one lower-sealed tube (1′) sealed by said lower cap 8.
The device according to the present invention further comprises a filling means 15 for said at least one lower-sealed tube 1′. The filling means 15 is arranged above the plate 23 of the carousel 22 and arranged to discharge said sterile formulation to be injected into said at least one lower-sealed tube 1′ to form at least one lower-sealed and filled tube 1″. The filling is carried out in the tube 1′ which is located in the housing 24 in position D according to the embodiment shown. The device according to the present invention further comprises a supply means for inert gas, preferably connected to the filling means.
The device also comprises a supply means 12, 14 for a series of upper caps 7, located above said plate 23 of the carousel 22 and arranged to seal the upper orifice 3 of the lower-sealed and filled tube 1″ by introducing at least partially at least one cap 7 of said series of upper caps 7 into the upper orifice 3 of said at least one lower-sealed and filled tube 1″ to form at least one sealed and filled tube 1′″.
Additionally, the device comprises a supply means 16 for at least one nozzle 9, arranged to supply a nozzle 9 to be connected to said at least one sealed and filled tube 1′″ and a collecting means 18 for said at least one assembled and filled container 40 for needle-free injection devices. In the embodiment shown in
The robotic arm 32 connects the sealed and filled tube 1′″ to the nozzle 9 by transporting it from the housing in position G into the tray 47 on the distribution table 31. The sealed and filled tube 1′″ connected to its nozzle 9 forms the container 40 which is collected by a collecting means which collects, in this embodiment, the tray comprising each nozzle 9 provided with a sealed and filled tube 1′″ and positions it on a conveyor 49. A sterile lid is added, either on the centring table or on the conveyor 49.
In one variant, a nozzle is supplied at the top of position G of the carousel and the tube located in the housing 24 of the carousel 22 in position G, which is a sealed and filled tube 1′″ is then connected to the nozzle outside the tray before being replaced there.
The tubs 28 are moved by a conveyor 43 to supply the nests 29 to the device, more particularly to the centring table 34. The nests 29 provided with tubes 1 are placed (“denested”) onto a centring table 34 by a first arm or robotic denesting arm 50. On the centring table 34, the tubes 1 are exposed protruding through the orifices of the nest 30 and rest on the lower flanges 6, allowing a second robotic arm 10 to take the tube 1 of the nest by the upper flange 5 thereof to house it in an orifice of a housing 24 of the rotating carousel 22 in position A.
The tube 1 is moved by rotating it along a movement trajectory, passing through a lower capping area 19 shown in the illustrated embodiment by position C, a filling area 20, shown in the illustrated embodiment by position D and an upper capping area 21, shown in the illustrated embodiment by position E. The lower caps 8 are supplied below the plate of the carousel 22 into the lower capping area 19 by the combination of a conveyor 11 and a vibrating bowl 42. The upper caps 7 are supplied above the plate of the carousel 22 into the upper capping area 21 by the combination of a conveyor 12 and a vibrating bowl 48. Between the lower capping area 19 and the upper capping area 21,
As illustrated in
In
The filling is carried out in the filling area 20 by discharging a sterile formulation to be injected into the upper orifice 3 of the lower-sealed tube 1′. The filling further comprises an area for injecting gas to remove oxygen and activate the solution. The amount of sterile formulation to be injected is predetermined and discharged using a pump via a filling needle 41 located above the carousel 22 to form the lower-sealed and filled tube 1″. The filling needle 41 is slidable and has a top resting position and a bottom filling position. The filling needle 41 is positioned above the meniscus of the sterile solution to be injected, i.e. the filling needle moves from the bottom upwards as the sterile solution to be injected is inserted into the lower-sealed tube 1′. The filling needle 41 is connected to a supply duct 38, which in turn is connected to a pump and supplied by an intermediate tank of sterile injectable solution, not shown in the figures, to form the filling means 41.
The upper cap 7 is introduced into the tube 1″ in the upper capping area 21 using a second piston 14 provided with a piston head moving from the top downwards using a movement system 33. The piston head is provided with the upper cap 7 and move vertically downwards to introduce the upper cap 7 into the tube 1″ above the upper meniscus of the sterile solution and from above the carousel 22 to form the sealed and filled tube 1″. Once the cap 7 has been introduced, the piston head returns to its top position without the upper cap 9. The upper cap supply 9 in the upper capping area 21 is formed by a second piston 14 provided with a piston head and a conveyor 12 connected to the vibrating bowl 48 and to the second piston 14. The upper capping area 21 further comprises an area for injecting inert gas (not shown) to remove oxygen and protect the solution by expelling carbon dioxide. The upper capping area 21 is coupled with an area for checking (not shown) the space created between the solution and the upper cap 9 by measuring the height between the top of the meniscus of the solution and the lower end of the upper cap. This checking area further comprises means for checking the position of the upper cap 9; preferably, the checking means is a camera. The height between the top of the meniscus of the solution and the lower end of the upper cap is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0.35 mm.
The lower capping, filling and upper capping steps are carried out consecutively by moving the carousel.
According to
In the embodiment shown in
When the machine is started, the first tube is supplied into the first housing in position A and the other housings are empty. The carousel 22 rotates one eighth of a turn and the first housing in position A moves to position B. The eighth housing in position H moves to position A. The seventh housing in position G moves to position H. The sixth housing in position F moves to position G. The fifth housing in position E moves to position F. The fourth housing in position D moves to position E. The third housing in position C moves to position D. The second housing in position B moves to position C.
Next, the first housing in position B moves to position C, the lower capping area, while the seventh housing in position H moves to position A and receives a new tube, the eighth housing is then is position B, the sixth housing is then in position H, the fifth housing is then in position G, the fourth housing is then in position F, the third housing is then in position E, the second housing in then in position D. In sequence, the carousel rotates another eighth of a turn and the first housing in position C moves to position D (the filling area 20), the eighth housing in position B moves to position C, the seventh housing in position A moves to position B, the sixth housing in position H moves to position A, the fifth housing in position G moves to position H, the fourth housing in position F moves to position G, the third housing in position E moves to position F, the second housing in position D moves to position E.
In continuous operation, the fifth tube is supplied to the first housing in position A, the fourth tube is in position C (3rd housing), i.e. in the lower capping position. The third tube is in position D (4th housing) i.e. in the filling position and the second tube is in position E (5th housing), i.e. in the upper capping position. The first sealed and filled tube is in position G (7th housing) to be supplied to the nozzle placement area outside the carousel. Positions B, F and H (second housing, sixth housing and eighth housing) remain free.
It is to be understood that the present invention is in no way limited to the embodiments described above and that modifications may be made without departing from the scope of the appended claims.
For example, the method according to the present invention may be implemented in a device comprising a clamp for gripping a tube, said clamp performing a rotational movement between at least two positions. Advantageously, the tube is moved by a circular movement between a first position and a second position. The first position is provided to introduce the lower cap and/or for filling to obtain a lower-sealed and/or filled tube. In another embodiment, the position for introducing the lower cap is different from the filling position. The second position is provided to introduce the upper cap to obtain a sealed and filled tube.
| Number | Date | Country | Kind |
|---|---|---|---|
| BE2020/5920 | Dec 2020 | BE | national |
| FR2013192 | Dec 2020 | FR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/085429 | 12/13/2021 | WO |
