WO2022128884A1

WO2022128884A1 - Method for assembling and filling containers for a needleless injection device

Info

Publication number: WO2022128884A1
Application number: PCT/EP2021/085429
Authority: WO
Inventors: Doezval L'HERYENAT
Original assignee: Cenexi - Laborathoires Thissen; Phixen Sas
Priority date: 2020-12-14
Filing date: 2021-12-13
Publication date: 2022-06-23
Also published as: US20240025578A1; EP4259527A1; CA3201395A1

Abstract

A method and device for assembling and filling containers for a needleless injection device, each container comprising: a tube (1), an upper stopper (7), a lower stopper (8) and a nozzle (9), the containers being arranged such that, once assembled and filled with a sterile pharmaceutical formulation to be injected, they are subsequently introduced into an auto-injection actuator, the aseptic carousel filling method comprising the steps of: supplying (10) tubes; supplying (11) lower stoppers; placing (13) lower stoppers, forming a tube which is closed off at the bottom; filling (15) the tube with a sterile formulation, forming a tube which is closed off at the bottom and filled; supplying (12) upper stoppers; closing off (14) with an upper stopper, forming a closed-off and filled tube; supplying (16) nozzles; placing the closed-off and filled tube in a nozzle to form an assembled and filled container for a needleless injection device; and collecting (18) the assembled and filled container for an injection device.

Description

METHOD FOR ASSEMBLING AND FILLING CONTAINERS FOR A NEEDLE-FREE INJECTION DEVICE Technical field The present invention relates to a device and a method for assembling and filling containers for a needle-free injection device with sterile pharmaceutical products. More precisely, the device and the method which are the subject of the invention apply to the assembly and to the automated industrial filling of a sterile solution in a container such as a tube. Technological background Traditionally, the vast majority of drugs were packaged in vials called “vials” (glass or sometimes plastic bottles). In some cases the vials contained the drugs in solution while in others they were in a solid state and had to be reconstituted with a solution to make an injectable drug solution. In the latter case, the drugs were administered to the patient after reconstitution by a doctor or pharmacist in a glass syringe. This method involved, on the one hand, a risk of dosage error both in terms of reconstitution and in terms of of the injectable dose, on the other hand a risk of contamination of the sterile solution. For decades, to overcome this risk, manufacturers began to package their product in pre-filled, ready-to-use administration devices. These delivery devices typically contain a single dose. The other advantage of prefilled devices is the fact of saving the active ingredient, which is used in less quantity. These days, most prefilled delivery devices have a glass or plastic tube that holds the drug solution, like prefilled syringes. The ISO 11040 standard defines pre-filled syringes. It describes pre-filled preassembled syringes as well as plunger caps and rods. And this applies to both glass and plastic syringes. A pre-filled syringe is a container filled with the injectable product, ready for injection. The syringe body is a cylindrical glass body with an end on which the needle will be fixed and a collar. A pre-filled sterilized pre-assembled syringe is a sub-assembly where each element has undergone pre-treatment, consisting of a syringe body and a closure system at the end on which the needle will be fixed. The sub-assembly must have been pretreated by the application of at least one of the following steps: assembly/lubrication of a needle, final washing/reduction of pyrogens, drying, application of a lubricant on the internal surface, sealing of the syringe with a closure, packaging and sterilization system. In other words, the pre-filled sterilized pre-assembled syringe comprises the cylinder body but the collar surrounding the orifice opposite the syringe body with respect to the end provided with the closure system is free. This orifice will later be used for filling the syringe and will then receive the plunger stopper, commonly called the piston seal, as well as the rod. In the case of pre-filled sterilized pre-assembled syringes, the responsibility for the above steps related to the injectable product lies with the primary packaging material manufacturer. After assembling the needle guard on the syringes, the pre-assembled syringes are placed in so-called nests. A nest is a support, often made of plastic, with holes for receiving syringes or other containers with an upper opening. The nests are then placed in plastic containers called tubs. The syringes placed in the nest are protected by a separating film and the tub is sealed by a stopper. The assembly is then double or triple wrapped to ensure a sterile barrier system. This makes it possible to deliver pre-filled sterilized pre-assembled syringes to pharmaceutical companies for subsequent filling or to contract companies for the same filling purposes. The growing worldwide prevalence of chronic, lifestyle-related diseases is also increasing the demand for prefilled delivery technologies. In the case of regular or even daily treatment, it is important to develop treatments that can be administered simply and/or painlessly by the patient himself, directly at home. The advantage of pre-filled devices is to eliminate the drug preparation step and therefore removes the risk of contamination linked to this preparation. On the other hand, many drawbacks remain, such as the disposal of syringes with their needles, the occurrence of broken needles, the “fear of needles”, as well as the risk of infection at the injection site. In recent years, many efforts have been made in research in the field of transdermal injection devices without needles or equipped with micro-needles. These needleless injection devices inject the drug substance under the skin by a blast or under high pressure. The sterile containers used in these needleless transdermal injectors are generally tubes sealed on both sides by removable caps. For example, the company Crossject and its pre-filled, single-use needle-free injection device Zeneo® which propels the solution in less than a tenth of a second through the skin (subcutaneous) or through the muscles (intra- muscular). The market for prefilled administration devices continues to grow, driven on the one hand by increased patient needs and on the other hand by the pharmaceutical industry seeking to reduce costs and increase efficiency. In recent years, these portable devices (“wearables”) are therefore developing, which also increases the demand for pre-filled devices. PRIOR ART The state of the art of automatic aseptic filling machines for syringe bodies is well known. Glassmakers manufacture and supply glass tubes with an opening intended to receive a liquid. The tubes or syringe body are arranged on a nest, namely a plastic support provided with holes for receiving tubes. The supports are then placed in tubs, namely transport containers, which are covered with a film of synthetic material, themselves packaged in one or more bags of synthetic material. The containers are sterilized, sent, then received by the pharmaceutical company or the subcontractor who unpacks the tubs in an aseptic environment. The nests are thus taken out of their tubs and either the containers or the nests are then placed in a loading space allowing the containers to be fed to an automatic filling machine organized in length. The loading space is located upstream of the filling area. In the filling zone, the tube of the syringe, sealed at the lower level, is filled through the upper orifice from the bottom of the tube by a descending-rising injector with adjustable stroke. Once the tube is filled, it is then plugged in a plugging zone, generally by inserting the plunger stopper, downstream of the filling zone. All of the loading, feeding, filling and capping zones follow one another in a linear machine. These machines have the disadvantage of requiring bulky and expensive infrastructures to set up all the elements of the linear chain for obtaining filled tubes. The terms "corked(s)" and "corked(s)" or "corked(s)" and "corked(s)" or even "grade(s)" and "class(es)" or "vibrant(s) and "vibration(s)" are used interchangeably in this patent application. Document EP3074313 discloses a sterile packaging installation for dermo-cosmetic or galenic preparations, in which the preparation is placed in a discharge hopper in the shape of a cone or an inverted pyramid serving as a funnel to fill the container. The container is brought under the hopper by a transfer device. The whole facility is in a sterile enclosure with an ultra-filtered air blower from the ceiling to the floor of the enclosure to produce a flow of protective air against particles around the fill area. Document EP3493783 discloses a line for the aseptic distribution of pharmaceutical products, such as for example solutions to be packaged in prefilled injectable syringes. Dispatch is performed in a sterile grade A area confined in an isolator. The grade A zone is surrounded by a grade C zone in which the operators necessary for the operation of the line work. The isolator is equipped with three hydrogen peroxide vapor generation systems to perform decontamination of surfaces in the insulator. The laminar flow isolator helps maintain a grade A sterile environment. Fluidized air allows air treatment to protect critical areas by controlling the risks of microbiological and particulate contamination and cross-contamination. The air is filtered by absolute filters and a pressure cascade is maintained. The isolator is equipped with glove boxes to allow handling in grade A by authorized persons in the context of machine operation or an unscheduled maintenance intervention. The syringes used are received ready to use, that is to say supplied in sterile packaging inside sealed tubs. The tubs are introduced into the isolator via a conveyor and are surface sterilized by means of ionizing radiation in order to be introduced into the grade A area. Once this step is completed, the tubs are uncapped 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, previously cleaned and sterilized in place. This solution is then filtered before being distributed in the syringes. After the filling station, the filled syringes then arrive at the capping station where a piston seal is inserted into the body of the syringe. This system guarantees the maintenance of the sterility of the components after sterilization 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 costs of filling related to the size of the installations and the personnel required for handling. All these methods make it possible to fill a container, one end of which is constitutively closed, as in syringes or in vials. These methods are therefore not applicable to through-tubes. However, given the growing demand for transdermal injectors without needles, there is therefore a need to provide a process for filling through tubes, in the pharmaceutical field, while respecting the sterility of the components. Unfortunately, at this stage, although needle-free medical devices are booming, the current demand concerns medium-sized batches and it is difficult to envisage developing very long, very expensive installations, requiring a lot of investment for the implementation. implementation of a process for filling a single type of container. Brief summary of the invention The object of the invention is to provide a method for assembling and filling containers which can be implemented with a compact installation, less expensive and limiting the risks of particulate and microbiological contamination. To solve this problem, there is provided according to the invention a method for assembling and filling z containers for a needleless injection device, each container comprising: - a tube comprising a tubular wall defining an upper orifice and a lower orifice , an upper flange extending peripherally from the tubular wall around the upper orifice towards the outside and optionally a lower flange extending peripherally from the tubular wall around the lower orifice, an upper plug arranged to be housed in said upper orifice and a lower plug arranged to be housed in said lower orifice, - a nozzle arranged to house said tube, said containers being arranged to then be, once assembled and filled with a sterile formulation for pharmaceutical use to be injected, subsequently introduced into an auto-injection actuator, in particular with explosive discharge, the aseptic filling process comprising the steps of: (i) feeding a series of z tubes, (ii) feeding a series of caps lower plugs, (iii) placing lower plugs during which at least one lower plug is inserted at least partially into said lower orifice of a tube of said series of tubes to form at least one tube lower closed by said lower plug, (iv ) filling said at least one lower closed tube by pouring said sterile formulation to be injected into said at least one lower closed tube, to form er at least one lower closed and filled tube, (v) a supply of a series of upper stoppers, (vi) a closing of the upper orifice of said lower closed and filled tube by an introduction at least partially of at least one plug of said series of upper plugs into the upper orifice of said at least one lower capped and filled tube to form at least one capped and filled tube, (vii) supplying a series of nozzles, (viii) placing said at least one at least one tube closed and filled in at least one nozzle of said series of nozzles, to form at least one at least one assembled and filled container for a needleless injection device, and (ix) a collection of said at least one assembled and filled container for an injection device, said steps (iii), (iv), (vi) being carried out in consecutively by at least one displacement of said at least one tube along a path of displacement passing through a lower plugging zone, and/or a filling zone and an upper plugging zone, said displacement of said at least one tube being performed by rotation , for example of at least one rotary carousel comprising a plate provided with a series of housings each provided with at least one through hole and with an upper wall, said at least one supplied tube being placed in a housing, said rotation said carousel being arranged to give said at least one tube said movement along the aforesaid movement path. The term “aseptic” is understood to mean, within the meaning of the present invention, a treatment which preserves the sterility of the components and products previously sterilized. An aseptic process consists in maintaining the sterility of a product, in a controlled environment and defined by 4 grades of controlled atmosphere zones: A, B, C, D defined by the European Pharmacopoeia or their equivalent with the American Pharmacopoeia. By the term "sterile" is meant, within the meaning of the present invention, a treatment which results in the maximum universal probability of a single non-sterile unit (PNSU) out of 10 ⁶ units. The term "grade A" means, within the meaning of the present invention, grade A as defined in annex 1 of 2008 in the document Eudralex, 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). The term "grade B" means, within the meaning of the present invention, grade B as defined in annex 1 of 2008 in the document Eudralex, 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. The terms "grades C and D" mean, within the meaning of the present invention, grades C and D as defined in annex 1 of 2008 in the document Eudralex, 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 The term “sterile formulation for pharmaceutical use” means, within the meaning of the present invention, any sterile substance used for its curative or preventive properties with regard to diseases or symptoms, which can be administered to the human body or to the animal body. The term “pharmaceutical” within the meaning of the present invention therefore qualifies both substances for human use and for veterinary use. As can be seen, according to the present invention, the method comprises a step of placing bottom plugs during which at least one bottom plug is introduced at least partially into said bottom orifice of a tube of said series of tubes to form at least an inferiorly sealed tube. Then, once closed at the lower level, the tube is then filled by pouring out a sterile formulation to be injected before closing the upper orifice of the tube passing through below closed and filled with an upper stopper. In this way, it is possible to aseptically fill any type of containers having an opening on either side of the container body as long as the sterility of the discharged formulation is maintained during the critical stages. By the terms “critical step” is meant, within the meaning of the present invention, a step where the formulation is exposed to the open air. According to the present invention, unlike syringe filling lines where all the actions are carried out from top to bottom, namely pouring the pharmaceutical solution into the syringe and then introducing the plunger stopper therein through the same upper orifice, it has been made possible to act on the through tube on the one hand from the top, but also from the bottom of the tube. Indeed, according to the present invention, the lower stopper is introduced through the lower orifice while the filling and placement of the upper stopper is implemented through the upper orifice. The introduction of the lower stopper through the lower orifice, which must be correctly oriented and fed in synchronization with the tube supply of the lower stopper zone, is all the more surprising since one of the main constraints is to remain in a small footprint. As can be seen, the lower stopper is introduced at least partially into the lower orifice of the tube, which allows appropriate positioning of the stopper, reproducible from one tube to another. Indeed, if the lower stopper were introduced from the top and therefore through the upper orifice of the tube, the positioning of the lower stopper would thus be random or in any case could not be perfectly positioned since the stopper would have to cross the entire height of the tube to be positioned on the lower part of the tube. The elasticity of the stopper does not facilitate its positioning within the tube, in particular in a glass tube in which it is constrained to ensure sealing. In addition, the elastic material of the stopper is covered with silicone, which would be deposited in the tube during its passage in a random and non-reproducible manner. There is significant friction when passing an elastic material through a glass tube of narrow diameter. Consequently, the introduction of a stopper from the top of the tube to reach the lower end of the latter could result in partial compressions of parts of this stopper, which could thus result in a stopper which is tilted, even returned in the tube, not evenly distributed and/or partially compressed and a deposit of silicone in the tube. This random positioning of the lower stopper in the case of an introduction from the top would therefore have an impact on the quantity of sterile formulation to be injected and on the positioning of the upper stopper (height, horizontality), or even on the tightness of the stopper. According to the present invention, the different steps of the filling process are implemented according to the rotation of the carousel. The rotary carousel comprises a plate provided with housings each provided with a through hole and with an upper wall. The carousel housing is intended to receive the tube. Depending on the case, the tube rests on the upper wall of the carousel by its upper flange which is wider than the tubular wall of the tube or by its lower flange, also wider than the tubular wall of the tube. The positioning of the tube in an orifice of a housing of the carousel makes it possible to maintain accessibility to the tube through the lower orifice and/or the upper orifice, which is not the case in the state of the art where access to the tube is only through the upper hole. According to the present invention, the introduction of the bottom stopper through the lower orifice of the tube is permitted on the one hand thanks to the orifice of the housing of the carousel and on the other hand by the rotation of the carousel allowing the tube to be moved to the different action zones. Indeed, the combination of the rotary carousel and the fact that each housing of the carousel has an orifice makes it possible to carry out actions from the top and from the bottom of the tube while leaving the lower orifice and the upper orifice of the tube accessible. Thanks to the carousel, the filling and capping steps are carried out in sequence by moving the tube along a path of rotary movement of the carousel. The tube positioned in a housing moves along a circular trajectory and not along a linear trajectory which makes it possible to offset from each other the robotic arms which act to carry out the various steps of the method according to the present invention and which thus allows them mobility. adequate without the risk of collisions between robotic arms and greater flexibility in terms of the movement that the robotic arm can perform. In addition, the rotary carousel is suitable for smaller pharmaceutical installations and makes it possible to remain in a reduced space by giving access to the tubes from the top and from the bottom, unlike the linear filling lines of prefilled syringes already existing where the syringe barrels are accessible only from above. Then, according to the present invention, the sealed and filled tube is placed on a nozzle. The nozzle makes it possible to form with the tube an assembled and filled container ready to be inserted into a needleless injection device. The nozzle therefore allows adaptation of the tube within the needleless injection device. According to the present invention, the feeding of a series of tubes is carried out according to the steps of: a) Feeding of a conveyor by means of tubes each comprising a nest in which tubes are arranged through the orifices of the nest, b) A removal of the nest provided with these tubes by a first robotic arm, during which the upper collars of the tubes rest on an upper surface of the nest and a placement of the nest on a surface of a centering table following which the lower collars of the tubes rest on said surface and part of the tubular wall of the tubes is exposed projecting through the holes of the nest, c) a removal of at least one tube by gripping by means of a gripper positioned on a second robotic arm, moving the tube by setting the robotic arm in motion and placing the tube in a housing of the carousel. Alternatively, the method according to the present invention can also comprise steps of washing, depyrogenation and/or sterilization, in the case where the tubes of the nest are not ready for use. In an advantageous embodiment according to the invention, the zones chosen from among the supply zone, the lower plugging zone, the filling zone, the upper plugging zone and the collection zone, are occupied by a housing of the series of housings of the carousel, in such a way that the rotation of the carousel allows the passage of the housings of the series of housings from one area to another. Preferably, according to the invention, the number of housings in 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 number minimum areas. Advantageously, the number of slots in the series of slots is greater than 5 and in which one slot in the series of housing is positioned between two zones selected from the supply zone, the lower stopper zone, the filling zone, the upper stopper zone and the collection zone, provided or not with a tube. In an advantageous embodiment according to the invention, each tube sealed, filled and positioned in the collection zone is gripped by means of 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 a needleless injection device. Advantageously, according to the invention, the tray comprising the assembled and filled containers for a needleless injection device is placed in a tub by a moving means, for example by a fourth robotic arm or a conveyor. Preferably, according to the invention, each closed and filled tube is then positioned in a nozzle laying zone where a nozzle is associated with the closed and filled tube by supplying a nozzle by a nozzle means provided with a moving head from the bottom upwards and whose head, provided with the nozzle in the lower position, moves vertically upwards to place the nozzle when the head is in the upper position and form the assembled and filled container for a needleless injection device, and returns to its low position without the nozzle, the nozzle means being positioned under the carousel. The invention also relates to the lower plugging carried out in the lower plugging zone by supplying a lower plug by means of a first piston provided with a piston head moving from the bottom upwards and whose piston head , fitted with the cap in the lower position, moves vertically upwards in the lower hole of the housing of the tube to place the lower stopper there when the head is in the high position and form the lower closed tube, and returns to its lower position without the lower stopper, the first piston being positioned under the carousel. Preferably, the method according to the invention comprises an inert gas injection step before and/or during and/or after the lower plugging step allowing the elimination of oxygen. The inert gas is selected from nitrogen, argon and/or the like. The injection of inert gas makes it possible to avoid any degradation of the solution which will be injected, to reduce the effect of oxidation and to preserve the effectiveness of this solution. Another advantage resides in the fact that the through tube additionally allows a more efficient purging for an inert gas. In a particularly advantageous manner, a source of gas is connected directly to a gripper allowing the gripping of the tube as well as the injection of gas into any zone of the carousel, for example via a double-envelope gripper. In an advantageous embodiment according to the invention, the filling of the at least one inferiorly closed tube is carried out by pouring the sterile formulation to be injected into the at least one inferiorly closed tube by means of a filling needle arranged to pour a predetermined quantity according to a rate such that the predetermined quantity is discharged during a residence time T that is smaller or equal to the residence time of the lower closed tube in the filling zone, to form the at least one lower closed and filled tube, the needle filler 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 allowing the elimination of oxygen and/or allowing activating the solution. If the gas is an inert gas, it is chosen from nitrogen, argon and/or the like. If the gas is not an inert gas, for example to activate the solution, mention may be made of carbon dioxide. Particularly advantageously, a source of inert gas is connected directly to the filling needle allowing the injection of gas into any area of the carousel, for example via a dual-channel, in particular dual-channel, filling needle concentric. Advantageously, according to the invention, the filling needle is sliding and has a high rest position and a low 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 closed and filled tube using means for measuring the filling volume comprising a calibration unit and a high-precision measuring unit . In an advantageous embodiment of the method according to the invention, the upper plugging is carried out in the upper plugging zone by supplying an upper plug by means of a second piston provided with a piston head moving from the top towards the bottom and whose piston head, provided with the upper stopper in the high position, moves vertically downwards in the upper orifice of the lowerly sealed and filled tube, to place the upper stopper there when the head is in the lower position and form the tube closed and filled, and returns to its high position without the upper stopper, the second piston being positioned above the carousel. Preferably, the method according to the present invention comprises a step of inert gas injection before and/or during and/or after the upper plugging step allowing the elimination of oxygen and protecting the solution by expelling carbon dioxide. The inert gas is selected from nitrogen, argon and/or the like. The injection of inert gas makes it possible to avoid any degradation of the solution which will be injected, to reduce the effect of oxidation and to preserve the effectiveness of this solution. Advantageously, the method comprises, after the upper plugging step, a step of verifying the space created between the solution and the upper plug by measuring the height between the top of the meniscus of the solution and the lower end of the top cap. This verification step includes in practice a control of the positioning of the upper plug via a camera. The height between the top of the meniscus of the solution and the lower end of the upper plug is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0. .35mm. In a particularly advantageous manner, a source of gas is connected directly to a gripper allowing the gripping of the tube as well as the injection of gas into any zone of the carousel, for example via a double-envelope gripper. In an advantageous embodiment, the steps are carried out consecutively by continuous movement of the carousel plate. In an advantageous embodiment, the steps are carried out consecutively by discontinuous movement of the carousel plate. The invention also relates to a device for assembling and filling z containers for a needleless injection device, each container comprising: - a tube comprising a tubular wall defining an upper orifice and a lower orifice, an upper flange s extending peripherally from the tubular wall around the upper orifice towards the outside and optionally a lower flange extending peripherally from the tubular wall around the lower orifice, an upper plug arranged to be housed in the upper orifice and a lower plug arranged to be housed in the lower orifice, - a nozzle arranged to house the tube, the containers being arranged to then be, once assembled and filled with a sterile formulation to be injected, introduced into an auto-injection actuator, particular explosive discharge device, the device being composed of: - a rotating carousel comprising a plate provided with a series of housings each provided with at least one through orifice, - means for rotating the plate arranged to confer a rotation to the plate around an axis of rotation, - a means of feeding a series of z tubes arranged to feed at least one tube of the series of z tubes into at least one l housing of the carousel, - a means for feeding a series of lower plugs, located under the plate and arranged to feed a lower plug at least partially into the lower orifice of a tube of the series of tubes to form at least a tube lower closed by the lower stopper, - a means of filling the at least one lower closed tube, located above the plate and arranged to pour the sterile formulation to be injected into the at least one lower closed tube, to form at least at least one lower tube closed and filled, - a means of supplying a series of upper stoppers, located above the plate and arranged for the closing of the upper orifice of the tube lower closed and filled by at least partially introducing at least one plug from the series of upper plugs into the upper orifice of the at least one lower tube closed and filled to form at least one closed tube and filled, - a means for supplying at least one nozzle arranged to bring a nozzle to be associated with the at least one closed and filled tube, and - a means for collecting the at least one assembled and filled container for an injection device . Advantageously, according to the invention, the means for supplying a series of upper stoppers is located in an upper stopper zone and comprises a vibrating bowl arranged to contain a series of upper stoppers and position them in an insertion position, a second piston provided with a piston head arranged to move from top to bottom and introduce the at least one upper plug 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 bring the at least one upper plug into the position of insertion into the piston head of the second piston. In an advantageous embodiment according to the invention, the supply means of a series bottom plugs are located in a bottom plugging zone and comprise a vibrating bowl arranged to contain a series of bottom plugs 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 plug 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 bring the at least one lower plug into the insertion position at the piston head of the first piston. Advantageously according to the invention, the means for filling the at least one lowerly sealed tube comprises a reservoir of sterile injectable solution and a filling needle connected to the reservoir of sterile injectable solution by a supply tube, the needle being arranged to discharge a predetermined quantity according to a rate such that the predetermined quantity is discharged during a residence time T smaller than or equal to the residence time of the lower closed tube in the filling zone, the filling needle being positioned above the plate of the carousel. In an advantageous embodiment of the device according to the invention, the means for supplying a series of z tubes arranged to supply at least one tube of the series of z tubes in at least one housing of the carousel comprises: - A conveyor of tubs each comprising a nest in which tubes are placed through the orifices of the nest, the conveyor being arranged to bring the tubs to a nest feeding zone, - A first robotic arm arranged to pick up a nest provided with its tubes and placing it on a centering table comprising an upper surface, the lower flanges of the tubes resting on the surface and a part of the tubular wall of the tubes being exposed projecting through the holes of the nest when the nest is placed on the table of centering, - A second robotic arm arranged to pick up at least one tube by gripping the exposed projecting tubes. Advantageously according to the invention, the filling needle is sliding and has a high rest position and a low filling position, the fluid movement forming a filling curve. Preferably, according to the invention, the means for supplying at least one nozzle arranged to cause a nozzle to be associated with the at least one closed and filled tube, comprises a third robotic arm, equipped with a gripper, arranged to picking up each sealed and filled tube positioned in the collection zone and conveying it into a tube 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 a device needleless injection. In an advantageous embodiment of the invention, the means for supplying at least one nozzle arranged to cause a nozzle to be associated with the at least one closed and filled tube comprises means for supplying at least one nozzle by a nozzle means provided with a head moving from the bottom upwards and whose head, provided with the nozzle in the low position, moves vertically upwards to place the nozzle when the head is in the high position and form the container assembled and filled for a needleless injection device in a nozzle placement area of the carousel, and returns to its low position without the nozzle, the nozzle means being positioned under the carousel and where the collecting means comprises a third robotic arm , provided with a gripper, 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 closed and filled tube comprising a calibration unit and a high-precision measuring unit. Preferably, the lower sealing zone further comprises an inert gas injection zone allowing the elimination of oxygen. The inert gas is selected from nitrogen, argon and/or the like. The injection of inert gas makes it possible to avoid any degradation of the solution which will be injected, to reduce the effect of oxidation and to preserve the effectiveness of this solution. Another advantage resides in the fact that the through tube additionally allows a more efficient purging for an inert gas. Preferably, the filling also comprises a gas injection zone allowing the elimination of oxygen and/or the activation of the solution. If the gas is an inert gas, it is chosen from nitrogen, argon and/or the like. If the gas is not an inert gas, for example to activate the solution, mention may be made of carbon dioxide. Particularly advantageously, a source of inert gas is connected directly to the filling needle allowing the injection of gas into any area of the carousel, for example via a dual-channel, in particular dual-channel, filling needle concentric. Preferably, the upper sealing zone further comprises an inert gas injection zone allowing the elimination of oxygen and the protection of the solution by expelling carbon dioxide. The inert gas is selected from nitrogen, argon and/or the like. The injection of inert gas makes it possible to avoid any degradation of the solution which will be injected, to reduce the effect of oxidation and to preserve the effectiveness of this solution. Advantageously, the upper plugging zone is coupled to a zone for checking the space created between the solution and the upper plug by measuring the height between the top of the meniscus of the solution and the lower end of the upper plug. . This verification zone further comprises control means positioning of the top cap, preferably the control means is a camera. The height between the top of the meniscus of the solution and the lower end of the upper plug is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0. .35mm. Other embodiments of the device according to the invention and other embodiments of the method are indicated in the appended claims. Brief description of the drawings Other characteristics, details and advantages of the invention will become apparent from the description given below, without limitation and with reference to the drawings and the examples. FIG. 1A illustrates a tub fitted with its nest and a series of tubes. Figure 1B illustrates a nest comprising a plurality of sterile containers. Figure 2 is an overview of the container assembly and filling device for a needleless injection device explaining the main steps of the present invention. Figure 3 is a sectional view of the empty tube carousel feed device arranged in a nest and moved by a first robotic arm. Figure 4 is a sectional view of the empty tube removal by gripping by means of a gripper of a second robotic arm. FIG. 5 is a side view of the empty tube evacuation step after having fed the carousel by the first robotic arm. Figure 6 is an overview of the capping, filling and cap feeding steps. FIG. 7 is a view of the step for collecting the filled and sealed tubes by a third robotic arm followed by the assembly on the nozzles in the tray and the conveying of the tray filled with tubes filled and assembled on a nozzle. Figure 8 is a detailed view of the vibrating bowl. In the figures, identical or similar elements bear the same references. The list of references used is described below: 1 – tube 1' – lower closed tube 1'' – lower closed and filled tube 1'' – closed and filled tube 2 – tubular wall 3 – upper hole 4- lower hole 5 – upper collar 6 – lower collar 7 – upper cap 8 – lower cap 9 – nozzle 10 – feeding means 10 – second robotic arm 11 – conveyor or rail for lower caps 11 / 13 – lower cap feeding means 13 – first plunger for inserting the bottom plug 12 – conveyor or rail for upper caps 12 / 14 – upper cap feeding means 14 – second piston for upper cap insertion 15 – filling means 16 – nozzle feeding means 18 – collection means 19 – lower capping area 20 – filling area 21 – upper capping area 22 – rotating carousel 23 – plate 24 – housing 26 – rotation means 28 – tub 29 – nest 30 – receiving hole 31 – distribution table 32 – third robotic arm 33 – movement system 34 – centering table 37 – gripper 38 – feed tube 40 – assembled and filled container 41 – filling needle 42 – vibrating bowl 43 – conveyor 44 – sealing cap 44 – means of maintenance 45 – lid 46 – medicinal solution 47 – tray 48 – vibrating bowl 49 – conveyor 50 – first robotic arm (classically called “stripping arm”) 51 – gripping means of the first robotic arm 52 – gripper of the ^2nd robotic arm 53 – movement system Detailed description of an embodiment of the invention Other characteristics and advantages of the present invention will become apparent from the non-limiting description which follows, and with reference to the drawings. As mentioned above, the present invention relates to the field of needleless transdermal injection devices which give excellent results in terms of rapid and uniform distribution in the human body or in the animal body without really requiring expertise or presenting any risk. badly located injection. These needle-free injection devices inject the contained medicinal substance under the skin by an explosion or under high pressure. The medicinal substance is contained in a sterile container. The sterile container is inserted into a needleless transdermal injector. FIG. 1A illustrates a tub provided with its nest 29 and a series of tubes 1. The nest 29 is a support, often made of plastic material, provided with holes 30 for receiving tubes. The nest is placed in a tub 28 sealed by a sealing cap 44 which makes it possible to obtain a sterile barrier system. Each tube 1 comprises a tubular wall 2, an upper orifice 3, a lower orifice 4, an upper collar 5 extending peripherally from the tubular wall 2 around the upper orifice 3 and a lower collar 6 extending peripherally from the tubular wall 2 around lower orifice 4. FIG. 1B illustrates a nest 47 comprising a plurality of sterile containers, ready to be introduced into a transdermal injector actuator. As can be seen in Figure 1B, each sterile container is formed of a through tube 1 which is blocked on either side by two removable plugs. A lower stopper 8 is located in the lower orifice 4 of the tube 1. An upper stopper 7 is located in the upper orifice 3 of the tube 1. Between the two stoppers is the drug solution 46. The tube 1 plugged on both sides the other is positioned in a nozzle 9. The sterile containers provided with nozzles 9 are introduced into a tray 47 provided with a lid 45. FIG. 2 illustrates a device for assembling and filling containers for an injection device without needle according to the present invention. As can be seen, the device according to the invention comprises a rotary carousel 22 comprising a solid or pierced plate 23. The device according to the present invention also comprises a means 10 for feeding a series of z tubes 1 arranged to feed at least one tube 1 of said series of z tubes 1 into at least one housing 24 of said carousel 22. In the form embodiment illustrated in Figure 2, the carousel comprises 8 housings 24 which move as the rotation for each pass from position A to position B, position C, position D, position E, the position F, position G and finally the position H. The feed device 10 takes a tube 1 from the nest 29, positioned on a centering table 34. The tube is thus fed into the housing 24 in position A. The centering table 34 makes it possible to present the tube 1 to the second robotic arm 10 so that the second robotic arm 10 performs a single and unique movement. The table 34 allows the centering of the nest 29 containing a tube 1 plumb with the second robotic arm 10. The device according to the present invention also comprises a supply means 11, 13 of a series of lower plugs 8. The means feed 11, 13 is located under the plate 23 of the carousel and is arranged to feed a lower plug 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 lowerly closed tube (1') by said lower stopper 8. The device according to the present invention further comprises a means 15 for filling said at least one lowerly closed tube 1'. Filling means 15 is arranged above plate 23 of carousel 22 and arranged to pour said sterile formulation to be injected into said at least one lower closed tube 1' to form at least one lower closed 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 illustrated embodiment. The device according to the present invention further comprises an inert gas supply means, preferably connected to the filling means. The device also comprises a means 12, 14 for supplying a series of upper plugs 7, which is located above said plate 23 of the carousel 22 and arranged for closing the upper orifice 3 of the lower closed tube. and filled 1'' by at least partially introducing at least one stopper 7 of said series of stoppers upper 7 in the upper orifice 3 of said at least one tube lower closed and filled 1 '' to form at least one closed tube and filled 1 ''. The device further comprises a supply means 16 of at least one nozzle 9 arranged to bring a nozzle 9 to associate with said at least one tube closed and filled 1''' and a collection means 18 of said at least one container 40 assembled and filled for needleless injection device. In the embodiment illustrated in FIG. 2, the means for supplying at least one nozzle is a conveyor which brings a tray 47. The tray 47 comprising a series of nozzles 9 is brought onto a centering table 31. The centering table 31 will make it possible to present the nozzle 9 to the third robotic arm 32 so that the third robotic arm 32 performs a single and unique movement. The distribution table 31 allows the centering of the tray 47 containing a nozzle 9 plumb with the third robotic arm 32. The robotic arm 32 associates the closed and filled tube 1''' with the nozzle 9 by transporting it from the housing in position G in the tray 47 on the distribution table 31. The closed and filled tube 1''' associated with its nozzle 9 forms the container 40 which is collected by a collection means which collects in this embodiment the tray comprising each nozzle 9 provided with a closed and filled tube 1''' and positions it on a conveyor 49. A sterile cover is added, either on the centering table, or on the conveyor 49. In a variant, a nozzle is brought to height of position G of the carousel and the tube which is in the housing 24 of the carousel 22 in position G, which is a closed and filled tube 1''' is then associated with the nozzle outside the tray before be replaced. The tubs 28 are moved by a conveyor 43 to allow feeding of the nests 29 into the device, plus particularly on the centering table 34. The nests 29 provided with the tubes 1 are placed ("stripped") on a centering table 34 by a first arm or robotic stripping arm 50. On the centering table 34, the tubes 1 are projecting through the orifices of the nest 30 and resting on their lower flanges 6 allowing a second robotic arm 10 to take the tube 1 of the nest by its upper flange 5 to house it in an orifice of a housing 24 of the rotary carousel 22, in position A. The tube 1 is moved by rotation along a path of movement passing through a lower plugging zone 19, represented in the embodiment illustrated by position C, a filling zone 20, represented in the form of embodiment illustrated by position D and an upper capping zone 21, represented in the embodiment illustrated by position E. The lower caps 8 are fed below the carousel plate 22 into the lower capping zone 19 by the combination of a conveyor 11 and a vibrating bowl 42. The upper caps 7 are fed above the carousel plate 22 into the upper capping zone 21 by the combination of a conveyor 12 and a vibrating bowl 48. Between the lower plugging zone 19 and the upper plugging zone 21, FIG. 2 illustrates the filling zone 20 which comprises a filling means 15 provided with a filling needle 41 Once the tube is sealed and filled 1''', the tube 1''' (in position G) is then transported onto a tray 47 comprising the nozzles 9 by a third robotic arm 32. The filling needle 41 can be a needle with double channels, preferably a needle with concentric double channels making it possible to inject inert gas into each zone of the carousel. FIG. 3 is a cross-sectional view of the device for feeding the carousel of empty tubes arranged in a nest 29. The tubs 28 are moved by a conveyor 43 to allow the feeding of the nests 29 into the device, more particularly on the table of centering 34. The nests 29 provided with tubes 1 are placed on a centering table 34 by a first robotic arm 50 rotating. The first robotic arm or stripping arm comprises a gripping means 51 which grasps the nest 29 and places it on the centering table 34 before releasing it (“stripping”). Once placed on the centering table 34, the tubes 1 are exposed projecting through the orifices of the nest 30 and rest on their lower flanges 6 allowing a second robotic arm 10 to take the tube 1 from the nest by its upper flange 5 to accommodate it in an orifice of a housing 24 of the rotary carousel 22, in position A. According to the embodiment of the method, the gripping means for the robotic arms used is a gripper, but of course it is possible to use any other gripping means, such as suction cups. As illustrated in Figure 4, the tube 1 positioned in the nest 29 on the centering table 34 is then picked up by a second robotic arm 10, to be brought into a housing 24 of the carousel 22. The second robotic arm 10 comprises a gripper 52 which holds the tube 1 by its upper flange 5. The carousel comprises a plate 23 provided with a series of housings 24, each housing 24 is provided with a through hole 25 and an upper wall. The rotation of the carousel is permitted by means of rotation means 26 around the axis of rotation R of the carousel plate 22 allowing the tube 1 to move consecutively from the supply zone to the plugging zone. lower 19, the filling zone 20 and the upper capping zone 21, by bringing the tube positioned in position A, towards position B, then towards position C, etc., up to position G where it is collected according to the illustrated embodiment. In FIG. 6, the lower plugging is carried out in the lower plugging zone 19, i.e. when the tube is in position C according to the embodiment illustrated by bringing a lower plug 8 by means of a first piston 13 provided with a piston head moving from bottom upwards by means of a movement system 53. The head of the piston provided with the lower stopper 8 moves vertically upwards to introduce the lower stopper 8 into the lower orifice 4 of the tube 1 under the carousel 22 to form the lower closed tube 1'. When the stopper is inserted, the piston head returns to its low position without the lower stopper 8. During the positioning of the lower stopper, holding means 44 exert pressure on the upper part of the tube 1, in particular on the upper collar 5 The feeding of the lower corks 8 in the lower corking zone 19 comprises a vibrating bowl 42, which orients the cork in the correct orientation (top of the cork up and bottom of the cork down) and the cork is conveyed in the correct position up to the lower stopper zone 19. The polarity of the stopper allows it to be placed in the tube 1. The lower stopper supply is formed by the piston 13 provided with a piston head and the conveyor 11 connected to the vibrating bowl 42. The lower sealing zone 19 further comprises an inert gas injection zone allowing the elimination of oxygen. The filling is carried out in the filling zone 20 by pouring a sterile formulation to be injected into the upper orifice 3 of the lower closed tube 1'. The filling further comprises an inert gas injection zone allowing the elimination of oxygen and the activation of the solution. The quantity of sterile formulation to be injected is predetermined and is dispensed by means of a pump via a filling needle 41 which is located above the carousel 22 to form the lower closed and filled tube 1''. The filling needle 41 is sliding and has a high rest position and a low filling position. The filling needle 41 is positioned above the meniscus of the sterile solution to be injected, i.e. the filling needle 41 moves from the bottom upwards as the sterile solution to be injected is inserted into the tube inferiorly sealed 1'. The filling needle 41 is connected to a supply tube 38 itself connected to a pump and fed by an intermediate reservoir of sterile solution for injection, not shown in the figures, to form the filling means 41. The upper stopper 7 is introduced into the tube 1'' in the upper plugging zone 21 by means of a second piston 14 provided with a piston head moving from top to bottom by means of a moving system 33. The piston head is provided with the upper stopper 7 and moves downwards vertically to introduce the upper stopper 7 into the tube 1'' above the upper meniscus of the sterile solution and through the top of the carousel 22 to form the tube capped and filled 1''. When the plug 7 is inserted, the piston head returns to its high position without the upper plug 9. The supply of the upper plugs 9 in the upper plugging zone 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 plugging zone 21 further comprises an inert gas injection zone (not shown) allowing the elimination of oxygen and the protection of the solution in expelling carbon dioxide. The upper plugging zone 21 is coupled to a verification zone (not shown) of the space created between the solution and the upper plug 9 by measuring the height between the top of the meniscus of the solution and the lower end of the top cap. This verification zone further comprises means for controlling the positioning of the upper stopper 9, preferably the control means is a camera. The height between the top of the meniscus of the solution and the lower end of the upper plug is between 0.10 and 0.50 mm, preferably between 0.20 and 0.40 mm, preferably between 0.25 and 0. .35mm. The lower capping, filling and upper capping steps are carried out consecutively by moving the carousel. FIG. 5 is a side view of the empty tub 28 evacuation step after having fed the carousel 22 by the first robotic arm 50. The tubs 28 are moved by a conveyor 43 to allow the feeding of the nests 29 in the device, more particularly on the centering table 34. The nests 29 provided with the tubes 1 are placed on a centering table 34 by a first robotic arm 50 rotating. The first robotic arm or stripping arm comprises a gripping means 51 which grasps the nest 29 and places it on the centering table 34 before releasing it. Once placed on the centering table 34, the empty tube 28 is transferred to a parallel conveyor and leaves without these tubes 1. According to FIG. 7, the device also comprises a third robotic arm 32 fitted with a clamp 37 allowing move the sealed and filled tube 1''' from the carousel 22 towards a 2 ^nd centering table 31 where there is a nest or a tray 47. The nest or the tray, hereinafter generically called tray 47 comprises a series of occupied positions by nozzles 9. The filled and closed tube 1''' is positioned on the nozzle 9 located in the tray 47. The nozzle 9 is positioned in a predetermined manner in the tray 47 to form an assembled and filled container for a device for needleless injection. The centering table 31 will make it possible to present the nozzle 9 to the third robotic arm 32 so that the third robotic arm 32 performs a single and unique movement. The distribution table 31 allows the centering of the tray 47 containing a nozzle 9 directly above the third robotic arm 32. Once the tray 47 has been filled with the assembled and filled containers, it is evacuated from the centering table 31 towards the conveyor 49. In the embodiment illustrated in Figures 1 to 7, the number of slots x of the carousel is 8. These slots are arranged to be occupied by 5 tubes (y = 5) and are represented by positions A to H. The first housing corresponds to position A and the eighth housing to position H. Each position is spaced out by one eighth of a turn of the rotary carousel 22. A batch of containers to be produced comprises z tubes 1, divided into nests and tubs. When the machine is started, the first tube is fed into the first housing in position A and the other housings are empty. The carousel 22 performs an eighth of a turn and the first housing in position A switches to position B. The eighth housing in position H switches to position A. The seventh housing in position G switches to position H. The sixth housing in position F switches to position G. The fifth slot in position E goes to position F. The fourth slot in position D goes to position E. The third slot in position C goes to position D. The second slot in position B goes to position C. Then the first housing in position B goes to position C, the lower plugging zone, while the seventh housing in position H goes to position A and receives a new tube, the eighth housing is then in position B, the sixth housing is then in position H, the fifth slot is then in position G, the fourth slot is then in position F, the third slot is then in position E, the second slot is then in position D. In sequence, the carousel performs in core an eighth of a turn and the first housing in position C goes to position D (the filling zone 20), the eighth housing in position B goes to position C, the seventh housing in position A goes to position B, the sixth housing in position H goes to position A, the fifth slot in position G goes to position H, the fourth slot in position F goes to position G, the third slot in position E goes to position F, the second slot in position D goes to position E . In continuous operation, the fifth tube is fed into the first housing in position A, the fourth tube is in position C (3 ^rd housing), ie in the lower plugging position. The third tube is in position D (4 ^th housing), or in the filling position and the second tube is in position E (5 ^th housing), or in the upper capping position. The first filled and sealed tube is in position G ( ^7th housing) to be brought into the nozzle laying area outside the carousel. Positions B, F and H (second slot, sixth slot and eighth slot) remain free. It is understood that the present invention is in no way limited to the embodiments described above and that many modifications can be made thereto without departing from the scope of the appended claims. For example, it is possible to implement the method according to the present invention in a device comprising a gripper gripping a tube, said gripper performs 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 for the introduction of the lower stopper and/or the filler to obtain a lower closed and/or filled tube. In another embodiment, the position of the introduction of the lower stopper is different from the filling position. The second position is provided for the introduction of the upper stopper to obtain a sealed and filled tube.

Claims

"CLAIMS" 1. Method for assembling and filling z containers for a needleless injection device, each container comprising: - a tube (1) comprising a tubular wall (2) defining an upper orifice (3) and an orifice (4), an upper flange (5) extending peripherally from the tubular wall (2) around the upper orifice (3) towards the outside and optionally a lower flange (6) extending peripherally from the wall tubular (2) around the lower orifice (4), an upper plug (7) arranged to be housed in said upper orifice (3) and a lower plug (8) arranged to be housed in said lower orifice (4), - a nozzle (9) arranged to house said tube (1), said containers being arranged to then be, once assembled and filled with a sterile formulation for pharmaceutical use to be injected, subsequently introduced into an auto-injection actuator, in particular with explosive discharge, the pro aseptic filling procedure comprising the steps of: (i) a supply (10) of at least one tube of a series of z tubes (1) (ii) a supply (11) of a series of lower plugs (8 ) (iii) placement (13) of lower plugs (8) during which at least one lower plug (8) is introduced at least partially into said lower orifice (4) of a tube (1) of said series of tubes (1) to form at least one lower closed tube (1') by said lower stopper (8) (iv) filling (15) of said at least one lower closed tube (1') by pouring said formulation sterile to be injected into said at least one lower closed tube (1'), to form at least one lower closed and filled tube (1''), (v) a supply (12) of a series of upper stoppers, (vi ) a closure (14) of the upper orifice (3) of said lower closed and filled tube (1'') by at least partially introducing at least one stopper of said series of upper stoppers (7) into the orifice upper (3) of said at least one lower closed and filled tube (1'') to form at least one closed and filled tube (1'''), (vii) a supply (16) of a series of nozzles (9 ), (viii) placing said at least one closed and filled tube (1''') in at least one nozzle (9) of said series of nozzles, to form at least one assembled container assembled and filled container for a needleless injection device, and (ix) a collection (18) of said at least one assembled and filled container for an injection device, said steps (iii), (iv), (vi) being carried out in consecutively by at least one movement of said at least one tube (1) along a movement path passing through a lower stopper zone (19), and/or a filling zone (20) and an upper stopper zone (21) , said movement of said at least one tube (1) being effected by rotation, for example of at least one rotary carousel (22) comprising a plate (23) provided with a series of housings (24) each provided with at least a through orifice (25) and an upper wall, said at least one fed tube (1) being arranged in a housing (24), said rotation of said carousel (22) being arranged to impart to said at least one tube (1) said movement along the aforesaid movement path.

2. Method according to claim 1, wherein said feeding (10) of a series of tubes (1) is carried out according to the steps of a) Feeding a conveyor by means of tubes (28) each comprising a nest (29 ) in which tubes (1) are arranged through the orifices (30) of the nest (29), b) a removal of the nest (29) provided with these tubes (1) by a first robotic arm (50), during which the upper flanges (5) of the tubes (1) rest on an upper surface of the nest (29) and a placement of the nest (29) on a surface of a centering table (34) following which the lower flanges (6) of the tubes (1) rest on said surface and part of the tubular wall (2) of the tubes (1) is exposed projecting through the orifices of the nest (30), c) a removal of at least one tube by gripping the means of a gripper positioned on a second robotic arm (10), displacement of the tube (1) by setting the robotic arm (10) in motion and placing said tube (1) in a n housing (24) of said carousel (22).

3. Method according to claim 1, in which each of the zones chosen from the feed zone, the lower plugging zone (19), the filling zone (20), the upper plugging zone (21) and the collection, is occupied by a housing of said series of housings of the carousel (22), in such a way that the rotation of the carousel (22) allows the passage of the housings of the series of housings (24) from one zone to the other .

4. Method according to claim 3, in which the number of housings of the series of housings (24) 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 to 5 corresponding to the minimum number of zones.

5. Method according to claim 3, in which the number of slots in the series of slots (24) is greater than 5 and in which a slot in said series of slots is positioned between two zones chosen from among the supply zone, the lower stopper zone (19), the filling zone (20), the upper stopper zone (21) and the collection zone, provided or not with a tube.

6. Method according to any one of the preceding claims, in which each tube closed, filled and positioned (1''') in the collection zone is collected by means of a third robotic arm (32), provided with means of gripping, and is transported by the third robotic arm (32) into a tray (47) comprising a series of positions occupied by nozzles (9) at the predetermined position of said tube (1) on the nozzle (9) to which it is assembled to form an assembled and filled needleless injection device container.

7. Method according to claim 6, in which the tray (47) comprising the assembled and filled containers for the needleless injection device is placed in a tub (28) by a moving means, for example by a fourth robotic arm or a conveyor (49).

8. Method according to any one of claims 2 to 7, in which each closed and filled tube (1''') then positioned in a nozzle laying zone where a nozzle (9) is associated with said closed and filled tube ( 1''') by supplying a nozzle (9) by a nozzle means provided with a head moving from the bottom upwards and the head of which, provided with the nozzle (9) in the low position, moves vertically towards the up to place the nozzle (9) when the head is in the up position and form said assembled and filled container (40) for a needleless injection device, and returns to its down position without the nozzle (9), said nozzle means being positioned under the carousel (22).

9. Method according to any one of the preceding claims, in which the lower plugging (13) is carried out in the lower plugging zone (19) by supplying a lower plug (8) by means of a first piston (13 ) provided with a piston head moving from the bottom upwards and whose piston head, provided with the plug in the low position, moves vertically upwards in the lower orifice (25) of the said housing (24) of the tube ( 1) to place the lower stopper (8) therein when the head is in the high position and form the said lowerly closed tube (1'), and returns to its lower position without the said lower stopper (8), the said first piston (13) being positioned under the carousel (22).

10. Method according to any one of the preceding claims, in which the filling of said at least one lower closed tube (1') is carried out by pouring said sterile formulation to be injected into said at least one lower closed tube (1') at the means of a filling needle (41) arranged to discharge a predetermined quantity according to a rate such that the predetermined quantity is discharged during a residence time T smaller than or equal to the residence time of the lowerly closed tube (1') in the filling zone (20), to form said at least one lower closed and filled tube (1''), said filling needle (41) being positioned above the carousel (22).

11. The method of claim 10, wherein said filling needle (41) is sliding and has a high rest position and a low filling position.

12. Method according to any one of the preceding claims, in which the upper plugging is carried out in the upper plugging zone (21) by supplying an upper plug (7) by means of a second piston (14) provided with a piston head moving from top to bottom and whose piston head, fitted with the upper plug (7) in the high position, moves vertically downwards in the upper orifice (3) of the lower closed and filled tube ( 1''), to place the upper stopper (7) therein when the head is in the lower position and form the said closed and filled tube (1'''), and returns to its upper position without the said upper stopper (7), the said second piston (14) being positioned above said carousel (22).

13. Method according to any one of the preceding claims, in which the steps are carried out consecutively by continuously moving the plate (23) of the said carousel (22).

14. Method according to any one of the preceding claims, in which the steps are carried out consecutively by discontinuous displacement of the plate (23) of the said carousel (22).

15. Device for assembling and filling z containers for a needleless injection device, each container comprising: - a tube (1) comprising a tubular wall (2) defining an upper orifice (3) and a lower orifice (4 ), an upper flange (5) extending peripherally from the tubular wall (2) around the upper orifice (3) towards the outside and optionally a lower flange (6) extending peripherally from the tubular wall (2 ) around the lower orifice (4), an upper plug (7) arranged to be housed in said upper orifice (3) and a lower cap (8) arranged to be housed in said lower orifice (4), - a nozzle (9) arranged to house said tube (1), said containers being arranged to then be, once assembled and filled with a sterile formulation to be injected, introduced into a self-injection actuator, in particular explosive discharge, said device being composed of: - a rotating carousel (22) comprising a plate (23) provided with a series of housings (24) provided each of at least one through orifice (25), - means for rotating said plate (23) arranged to impart rotation to the plate (23) around an axis of rotation, - a means for feeding (10) of a series of z tubes (1) arranged to feed at least one tube (1) of said series of z tubes (1) into at least one housing (24) of said carousel (22), - a means of supply (11) of a series of lower plugs (8), located under said plate (23) and arranged to supply a lower plug (8) at least partly llement in the lower orifice (4) of a tube (1) of said series of tubes (1) to form at least one lower tube closed (1 ') by said lower plug (8), - a filling means ( 15) of said at least one lower closed tube (1'), located above said plate (23) and arranged to pour said sterile formulation to be injected into said at least one lower closed tube (1'), to form at least a bottom closed and filled tube (1''), - a supply means (14) of a series of upper plugs (7), located above said plate (23) and arranged for the closing of the upper orifice (3) of said lower tube closed and filled (1'') by at least partially introducing at least one stopper of said series of upper stoppers (7) in the upper orifice (3) of said at least one lower closed and filled tube (1'') to form at least one closed and filled tube (1''), - a supply means (16) of at at least one nozzle (9) arranged to cause a nozzle (9) to be associated with said at least one closed and filled tube (1'''), and - a collection means (18) of said at least one assembled and filled container for injection device (40).

16. Device according to claim 15, in which said supply means (12) of a series of upper plugs (7) is located in an upper plugging zone (21) and comprises a vibrating bowl (48) arranged to contain a series of top plugs (7) and position them in an insertion position, a second piston (14) provided with a piston head arranged to move from top to bottom and insert said at least one top plug (7 ) in the upper orifice (3) of said at least one tube (1) of said series of tubes and a conveyor (12) connected to said vibrating bowl (48) and to said second piston (14), said conveyor (12) being arranged to bring said at least one upper plug (7) into the position of insertion to said piston head of said second piston (14)

17. Device according to claim 15, in which said supply means (11) of a series of lower plugs (8) are located in a lower plugging zone (19) and comprise a vibrating bowl (42) arranged to contain a series of lower plugs (8) and positioning them in an insertion position, a first piston (13) provided with a piston head, arranged to move from the bottom upwards and to introduce said at least one lower plug ( 8) in the lower orifice (4) of said at least one tube (1) of said series of tubes and a conveyor (11) connected to said vibrating bowl (42) and to said first piston (13), said conveyor (11) being arranged to bring said at least one lower plug (8) into the position of insertion to said piston head of said first piston (13).

18. Device according to one of claims 15 to 17, wherein the filling means (15) of said at least one lower closed tube (1 ') comprises a reservoir of sterile solution for injection and a filling needle (41) connected to said reservoir of sterile solution for injection through a supply tube 38, said needle (41) being arranged to discharge a predetermined quantity according to a rate such that the predetermined quantity is discharged during a residence time T less than or equal to the residence time of the lower closed tube (1') in the filling zone (20), said filling needle (41) being positioned above the plate (23) of the carousel (22).

19. Device according to one of claims 15 to 18, wherein the supply means (10) of a series of z tubes arranged to supply at least one tube (1) of said series of z tubes in at least one housing (24) of said carousel (22) comprises: - A conveyor (43) of tubes (28) each comprising a nest (29) in which tubes (1) are arranged through the orifices of the nest (30), said conveyor (43) being arranged to bring said tubs (28) to a nest feeding zone (34), - A first robotic arm (50) arranged to pick up a nest (29) fitted with its tubes (1) and place it on a centering table (34) comprising an upper surface, the lower flanges (6) of the tubes (1) resting on said surface and a part of the tubular wall (2) of the tubes being exposed projecting through the openings of the nest (30) when the nest (29) is placed on said centering table (34), - A second robotic arm (10) arranged to pick up at least one tube (1) by preh extension of the tubes exposed protruding.

20. Device according to claim 18 or claim 19, wherein said filling needle (41) is sliding and has a high rest position and a low filling position.

21. Device according to any one of claims 16 to 20, wherein said supply means (16) of at least one nozzle (9) arranged to bring a nozzle (9) to associate with said at least one closed tube and filled (1'''), comprises a third robotic arm (32), provided with a gripper, arranged to pick up each closed and filled tube (1''') positioned in the collection area and route it into a tub comprising a series of positions occupied by nozzles (9) at the predetermined position of said tube (1) on the nozzle (9) to be assembled to form an assembled and filled container for a needleless injection device (40).

22. Device according to any one of claims 15 to 21, wherein said supply means (16) of at least one nozzle (9) arranged to bring a nozzle (9) to associate with said at least one closed tube and filled (1''') comprises supply means (16) of at least one nozzle (9) by a nozzle means provided with a head moving from the bottom upwards and the head of which, provided with the nozzle (9) in the lower position moves vertically upwards to place the nozzle (9) when the head is in the upper position and form said assembled and filled container for a needleless injection device (40) in a placement zone nozzle of the carousel (22), and returns to its low position without the nozzle, said nozzle means being positioned under the carousel (22) and wherein said collecting means (18) comprise a third robotic arm (32), provided with 'a gripper, arranged to pick up an assembled and filled container (1''') and transport it into a tray (47).