CA3201395A1 - Method for assembling and filling containers for a needleless injection device - Google Patents

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 DEVICE CONTAINERS
INJECTION WITHOUT NEEDLE
Technical area The present invention relates to a device and a method assembly and filling of containers for a device injection without needle, by sterile pharmaceutical products.
More precisely the device and the method which are the subject of the invention apply to automated industrial assembly and filling, of a sterile solution in a container such as a tube.
Technology background Traditionally, the vast majority of drugs was packaged in vials called rapes (glass bottle or sometimes plastic). In some cases the vials contained the drugs in solution while in others they were in solid state and had to be reconstituted with a solution to make a injectable medicinal 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 included on the one hand, a risk of dosage error both at the level of the reconstitution than at the level of the injectable dose, on the other hand a risk contamination of the sterile solution. For decades, to overcome this risk, manufacturers have begun to package their product in pre-filled, ready-to-use delivery devices.
These delivery devices typically contain a dose unique. The other advantage of prefilled devices is saving the active ingredient, which is used in less quantity.

2 Today, most delivery devices prefilled come with a glass or plastic tube that contains the medicinal solution, such as pre-filled syringes.
The ISO 11040 standard defines pre-filled syringes. She describes the pre-assembled pre-fillable syringes as well as the caps-pistons and rods. And this applies to both glass and plastic syringes.

A pre-filled syringe is a container filled with the product for injection, ready for injection. The syringe body is a shaped glass body cylindrical with one end on which the needle will be fixed and of a collar. A pre-filled sterilized pre-assembled syringe is a subset where each element has undergone a preprocessing, composed of a syringe body and of a closure system at the end on which will attach the needle. The subset must have been pretreated by applying 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, closure of the syringe with a closure system, packaging and sterilization. In other words, the sterilized preassembled syringe prefillable includes the cylinder body but the collar surrounding the orifice opposite the syringe body with respect to the end fitted with the closure system is free. This hole will be subsequently used for filling the syringe and will then receive the piston cap, commonly called a piston seal, and the rod.
In the case of sterilized preassembled syringes pre-fillable, responsibility for the above-mentioned steps relating to the injectable product is the responsibility of the packaging article manufacturer primary.
After assembling the needle guard on the syringes, the preassembled syringes are placed in so-called nests.

3 A nest is a support, often made of plastic, with holes for receipt of syringes or other containers with an opening superior. The nests are then placed in plastic bins called tubs. The syringes placed in the nest are protected by a film separator and the tub is sealed with a stopper. All is then double or triple wrapped in order to guarantee a system sterile barrier. This allows the syringes to be delivered pre-assembled prefillable sterilized bottles to pharmaceutical companies for their subsequent filling or to subcontracting companies for the same purposes filling.
The growing global prevalence of diseases chronic, lifestyle-related, also increases the demand for pre-populated administration technologies. In the case of treatment regular, even daily, it is important to develop treatments which can be administered in a simple and/or painless way by the patient himself, directly at home. The device advantage prefilled is to eliminate the drug preparation step and therefore eliminates the risk of contamination linked to this preparation.
However, many disadvantages remain, such as the disposal of syringes with their needles, the occurrence of needles broken, fear of needles, as well as the risk of infection at the site injection.
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 under the skin the drug substance by a deflagration or under high pressure. The sterile containers used in these transdermal injectors without a needle are usually tubes blocked on both sides by WO 2022/12888

4 removable caps. For example, the company Crossject and its 7eneo0 pre-filled, single-use needle-free injection device that propels the solution through the skin in less than a tenth of a second (subcutaneous) or through the muscles (intramuscular).
The market for prefilled administration devices continues its growth, driven on the one hand by the increased needs of patients and on the other share by the pharmaceutical industry, which seeks to reduce costs and increase efficiency. In recent years, these devices transportables ( wearables ) are therefore developing, which is increasing also the demand for prefilled devices.
Prior art It is well-known state-of-the-art machinery aseptic filling machines for syringe barrels. THE
glassmakers manufacture and supply glass tubes with an opening intended to receive a liquid. The tubes or syringe barrels are arranged on a nest, namely a plastic support provided with holes tube reception. The supports are then placed in tubs, namely transport containers, which are sealed with a film in synthetic material, themselves packed in one or more sachets in synthetic material. The containers are sterilized, shipped, and then received by the pharmaceutical company or the subcontractor who unpack tubs in an aseptic environment. The nests are like this taken out of their tubs and either the containers or the nests are then placed In a loading space allowing the supply of containers 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 level bottom is filled through the top port from the bottom of the tube by a descending-rising injector with adjustable stroke.

Once the tube is filled, it is then capped in a plugging zone, generally by inserting the plunger plug, downstream of the filling zone. All loading areas, feeding, filling and capping follow each other in a

5 linear machine. These machines have the disadvantage of requiring voluminous and costly infrastructures to set up all the elements of the linear chain for obtaining tubes full.
THE
terms clogged and corked or corking(s) and corking(s) or even grade(s) and class(es) or vibrating(s) and vibrating(s) are used in a way interchangeable in this patent application.
The document EP3074313 discloses an installation of sterile packaging for dermo-cosmetic preparations or galenic, in which the preparation is placed in a hopper of discharge in the shape of a cone or an inverted pyramid serving funnel to fill the container. The container is brought under the hopper by a transfer device. The entire installation is located in a sterile enclosure fitted with an ultra-filtered from the ceiling to the floor of the enclosure intended to produce an air flow of particle protection around the filling area.
EP3493783 discloses a distribution line aseptic of pharmaceutical products, such as for example solutions to be packaged in pre-filled injectable syringes. There distribution is carried out in a sterile grade A area confined in a insulator. The grade A area is surrounded by a grade C area in which evolve the operators necessary for the operation of the line. The isolator is equipped with three steam generation systems hydrogen peroxide for carrying out decontamination of

6 surfaces in the insulator. The laminar flow isolator allows maintain a sterile Grade A environment. Fluidized air allows for a air treatment to protect critical areas by controlling risks of microbiological and particulate contamination and cross contamination. The air is filtered by absolute filters and a waterfall pressure is maintained. The isolator is equipped with glove boxes for allow handling in grade A by persons authorized in as part of machine operation or maintenance unexpected. Used syringes are received ready to use i.e. supplied in sterile packaging inside tubs waterproof. 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 dispatch machine is supplied with solution by a direct pipe, previously cleaned and sterilized in place. This solution is then filtered before to be distributed in the syringes. After the filling station, the filled syringes then arrive at the capping station where a plunger seal is inserted into the syringe body. This system guaranteed 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 area of filling. Another disadvantage of these devices is the cost of filling related to the size of the facilities and the personnel required to handling.

7 All these processes make it possible to fill a container whose one end is constitutively closed, as in syringes or in the vials. These processes are therefore not applicable to tubes crossings.
However, given the growing demand for injectors without needles, so there is a need to provide a process for filling through tubes, in the field pharmaceutical, respecting the sterility of the components.
Unfortunately, at this stage, although medical devices without needle are booming, current demand is for batches of medium size and it is difficult to envisage developing very long, very expensive installations, requiring a lot investment for the 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 of assembling and filling of 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 of assembling and filling device containers needleless injection, each container comprising:
- a tube comprising a tubular wall defining an orifice upper and a lower orifice, an upper flange extending peripherally of the tubular wall around the upper orifice towards the outside and possibly a lower collar extending peripherally from the tubular wall around the lower orifice, an upper plug arranged to be housed in

8 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, particular explosive discharge, the aseptic filling process comprising the steps of:
(i) a supply of a series of z tubes, (ii) a feed from a series of bottom plugs, (iii) a bottom plug placement during which at least a bottom plug is inserted at least partially into said lower orifice of a tube of said series of tubes for form at least one lower tube closed by said bottom cap, (iv) a filling of 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 at least minus one lowerly sealed and filled tube, (y) a supply of a series of top caps, (vi) a blockage of the upper orifice of said tube lowerly closed and filled by an introduction at least partially of at least one stopper of said series of top plugs in the top orifice of said at least one lower tube sealed and filled to form at least one tube closed and filled, (vii) a supply of a series of nozzles, (viii) placing said at least one sealed and filled tube in at least one nozzle of said series of nozzles, to form at least

9 least one assembled and filled device container needle-free injection, and (ix) collection of said at least one assembled and filled container for injection device, said steps (iii), (iv), (vi) being carried out in such a way consecutive by at least one displacement of said at least one tube according to a path of movement passing through a clogging zone bottom, and/or a filling zone and a plugging zone upper, said displacement of said at least one tube being effected 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 orifice and an upper wall, said at least one tube powered being disposed in a housing, said rotation of said carousel being arranged to impart to said at least one tube said movement according to the aforesaid movement trajectory. By the term aseptic, we means, within the meaning of the present invention, a treatment which preserves the sterility of previously sterilized components and products. A
aseptic process consists in maintaining the sterility of a product, in a environment controlled and defined by 4 grades of atmosphere zones controlled: A, B, C, D defined by the European Pharmacopoeia or their equivalent in the United States Pharmacopeia.
By the term sterile, we mean, within the meaning of the present invention, a treatment that results in the universal maximum probability a single non-sterile unit (PNSU) out of 106 units.
By the terms grade A, we mean, within the meaning of this 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 by page 2 and page 3 (table).
By the terms grade B, we mean, within the meaning of this invention, grade B as defined in annex 1 of 2008 in the 5 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 by page 3.
The terms grades C and D mean, within the meaning of

10 present invention, grades C and D as defined in appendix 1 of 2008 in Eudralex, The Rules Governing Medicinal Products in the European Union, Volume 4, EU Guidelines to Good Manufacturing Pratice, Medicinal Products for Human and Veterinary Use, grades C and D are defined on page 3.
By 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 against diseases or symptoms, which can be administered to the human body or to the animal body. THE
pharmaceutical term within the meaning of the present invention therefore qualifies both substances for human and veterinary use.
As can be seen, according to the present invention, the method includes a step of placing bottom plugs during which at least one bottom plug is introduced at least partially in said lower hole of a tube of said series of tubes to form at least one lower closed tube. Then once closed at the lower level, the tube is then filled by pouring a sterile formulation to be injected before closing the upper orifice of the tube crossing from below closed and filled with an upper stopper.
In this way, it is possible to aseptically fill any type of

11 containers having an opening on either side of the body of container as long as the sterility of the spilled formulation is maintained during critical stages.
The term critical stage means, within the meaning of present invention, a step where the formulation is exposed to the open air.
According to the present invention, unlike lines of syringe filling where all actions are performed from top to down, namely pouring the pharmaceutical solution into the syringe and then insert the plunger plug through the same upper hole, it was made possible to act on the through tube on the one hand from above, but also, from the bottom of the tube. Indeed, according to the present invention, the stopper lower is introduced through the lower orifice while the filling and the placement of the top plug is implemented through the orifice superior.
The introduction of the lower plug through the lower hole, which must be correctly oriented and fed in synchronization with the tube feed of the lower capping area is all the more surprising that one of the main constraints is to stay in a small footprint.
As can be seen, the bottom cap is introduced at least partially into the lower orifice of the tube, which allows proper positioning of the cap, reproducible from one tube to another. Indeed, if the lower stopper was introduced from the top And therefore through the upper orifice of the tube, the positioning of the stopper lower would thus be random or in any case could be not perfectly positioned since the cap should cross the entire height of the tube to be positioned on the lower part of the tube. The elasticity of stopper does not facilitate its installation within the tube, in particular in a glass tube in which it is forced to ensure the seal.

12 In addition, the elastic material of the stopper is coated with silicone, which would be deposited in the tube during its passage randomly and non reproductable. There are significant frictions when doing pass an elastic material in a glass tube of narrow diameter. By therefore, inserting a stopper through the top of the tube to reaching the low end of it could result in partial compressions of parts of this plug, which could thus have resulting in a cork that is tilted or even turned upside down in the tube, not homogeneously distributed and/or partially compressed and a deposit of silicone in the tube. This random positioning of the cork lower in the case of an introduction from the top would therefore have a impact on the quantity of sterile formulation to be injected and on the positioning of the top cap (height, horizontality), or even on sealing of the cap.
According to the present invention, the different stages of the process filling are implemented according to the rotation of the carousel. THE
rotary carousel comprises a plate provided with housings provided each with a through hole and a top wall. The accommodation of carousel 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 hole and/or the upper hole, which is not the case in the state of the art where access to the tube is made only by 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 in the different action zones.

13 Indeed, the combination of the rotating carousel and the fact that each housing of the carousel has an orifice allows actions to be carried out from the top and from the bottom of the tube, leaving the lower hole and the hole top of the accessible tube. Thanks to the carousel, the stages of filling and capping are carried out in sequence by movement of the tube along a path of rotary movement of the carousel. The tube positioned in a housing moves according to a circular trajectory and not according to a linear trajectory which makes it possible to shift the robotic arms from each other, which act to carry out the different steps of the method according to the present invention and which thus allows them an adequate mobility without risk of shocks between robotic arms and greater flexibility in terms of movement than the robotic arm can perform. In addition, the rotating carousel is suitable for pharmaceutical facilities of smaller sizes and allows to remain in a small footprint by giving access to the tubes through the top and bottom, unlike linear filling lines existing pre-filled syringes 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 a container assembled and filled ready to be inserted into a device needleless injection. The nozzle therefore allows the adaptation of the tube to the within the needleless injection device.
According to the present invention, the supply of a series of tubes is carried out according to the steps of:
a) Feeding a conveyor using tubs each comprising a nest in which tubes are arranged through the openings of the nest,

14 b) Sampling of the nest equipped with these tubes by a first robotic arm, during which the upper flanges of the tubes rest on an upper surface of the nest and a placement of the nest on a surface of a table of centering following which the lower flanges of the tubes rest on said surface and part of the wall tubular of the tubes is exposed projecting through the nest holes, c) A sample of at least one tube by gripping the means of a gripper positioned on a second arm robotized, a movement of the tube by setting movement of the robotic arm and placement of the tube in a slot in the carousel.
Alternatively, the method according to the present invention can also include steps of washing, depyrogenation and/or sterilization, in the event that the nest tubes are not ready to employment.
In an advantageous embodiment according to the invention, the zones chosen from the supply zone, the plugging zone bottom, the filling zone, the upper capping zone and the collection area, is occupied by a dwelling of the series of dwellings of the carousel, in such a way that the rotation of the carousel allows the movement of the dwellings of the series of dwellings from one zone to another.
Preferably, according to the invention, the number of housings in the series number of dwellings is equal to or greater than 2, preferably equal to or greater than to 3, preferably equal to or greater than 4, preferably equal to or greater to 5 corresponding to the minimum number of zones.
Advantageously, the number of slots in the series of slots is greater than 5 and in which a slot in the series of housing is positioned between two zones selected from the zone supply, the lower capping area, the filling area, the upper capping area and the collection area, whether or not fitted with a tube.
5 In an advantageous embodiment according to the invention, each tube sealed, filled and positioned in the collection area is seized by means of a third robotic arm, provided with gripping means, and is transported by the third robotic arm into a tray comprising a series of positions occupied by nozzles at the 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 needleless injection device is placed in a tub by a moving means, for example by a

15 fourth robotic arm or conveyor.
Preferably, according to the invention, each tube sealed and filled then positioned in a nozzle laying area where a nozzle is associated with the sealed tube and filled by supplying a nozzle by a means nozzle provided with a head moving from bottom to top and whose head, equipped with the nozzle in the low position, moves vertically towards the up to place the nozzle when the head is in the up position and form the assembled and filled container for 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 bringing a lower plug to the means of a first piston provided with a piston head moving from bottom upwards and whose piston head, fitted with the plug in position bass moves vertically upwards in the lower hole of the

16 housing of the tube to place the lower cap there when the head is in high position and form the inferiorly obturated tube, and returns to its low position without the lower cap, the first piston being positioned under the carousel.
Preferably, the method according to the invention comprises a step injection of inert gas before and/or during and/or after the step of lower plugging allowing the elimination of oxygen. The inert gas is selected from nitrogen, argon and/or the like. Inert gas injection makes it possible to avoid any degradation of the solution which will be injected, reduce the effect of oxidation and preserve the effectiveness of this solution. A
another advantage lies in the fact that the through tube also allows a more efficient purge for an inert gas. In a particularly advantageously, a gas source is connected directly to a clamp allowing the gripping of the tube as well as the injection of gas into any area of the carousel, for example via a double clamp envelopes.
In an advantageous embodiment according to the invention, the filling of the at least one lower closed tube is carried out by pouring of the sterile formulation to be injected into the at least one tube lowerly sealed by means of a filling needle arranged to discharge a predetermined quantity at a rate such that the predetermined quantity is discharged during a residence time T plus small or equal to the residence time of the lower closed tube in the filling zone, to form the at least one tube below closed and filled, the filling needle being positioned above the carousel.
Preferably, the method according to the invention comprises a step injection of gas before and/or during and/or after the step of filling allowing the elimination of oxygen and/or allowing

17 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, we can cite carbon dioxide. Of particularly advantageously, a source of inert gas is connected directly to the filling needle allowing the injection of gas in any area of the carousel, for example via a needle dual-channel filler, in particular dual-channel concentric.
Advantageously, according to the invention, the filling needle is sliding and has a high rest position and a low position filling, the fluid movement forming a filling curve.
Preferably, the method according to the invention comprises a step control of the filling volume of each tube below sealed and filled using means for measuring the filling volume comprising a calibration unit and a measurement unit with high accuracy.
In an advantageous embodiment of the method according to the invention, the upper plugging is carried out in the zone of upper stopper by supplying an upper stopper by means of a second piston with a piston head moving from top to bottom bottom and whose piston head, provided with the upper cap in position high moves vertically downward in the upper hole of the lower tube closed and filled, to place the upper stopper when the head is in the low position and form the tube closed and filled, and returns to its high position without the top plug, 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 stage allowing the elimination of oxygen and

18 protecting the solution by expelling carbon dioxide. The gas inert is chosen from nitrogen, argon and/or the like. Gas injection inert prevents any degradation of the solution that will be injected, reduce the effect of oxidation and preserve the effectiveness of this solution.
Advantageously, the method comprises, after the step of upper capping, a verification step of 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 stopper superior. This verification step includes in practice a check the positioning of the top cap via a camera. The height between the top of the meniscus of the solution and the lower end of the top 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. So particularly advantageous, a source of gas is connected directly to a clamp allowing the gripping of the tube as well as the injection of gas in any area of the carousel, for example via a clamp double envelopes.
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 discontinuous movement of the plate of the carousel.
The invention also relates to a device for assembling and filling z containers for needleless injection device, each container including:
- a tube comprising a tubular wall defining an orifice upper and a lower orifice, an upper flange extending

19 peripherally of the tubular wall around the upper orifice towards the outside and possibly 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 hole, - 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 a self-acting actuator injection, in particular with explosive discharge, the device being composed of:
- a rotating carousel comprising a plate provided with a series housings each provided with at least one through hole, - Means for rotating the plate arranged to impart rotation to the plate around an axis of rotation, - a means of supplying a series of z tubes arranged for feed at least one tube of the series of z tubes into at least one carousel housing, - a means of supplying a series of lower plugs, located under the plate and arranged to supply a stopper at least partially in the lower orifice of a tube of the series of tubes to form at least one tube below closed by the lower cap, - a means for filling the at least one tube below sealed, located above the plate and arranged to discharge the sterile formulation to be injected into the at least one tube inferiorly closed, to form at least one lower closed tube and completed, - a means of supplying a series of upper plugs, located above the plate and arranged for the obturation of the upper orifice of the lower tube closed and filled with a introduction at least partially of at least one plug of the series of top plugs in the top hole of the at least one lower tube sealed and filled to form at least one tube 5 sealed and filled, - a supply means of at least one nozzle arranged to causing a nozzle to associate with the at least one capped tube and filled, and - a means for collecting the at least one assembled container and 10 filled for injection device.
Advantageously, according to the invention, the AVERAGE
supply of a series of upper plugs is located in an upper capping area and includes a vibrating bowl arranged to hold a series of top caps and the 15 position in an insertion position, a second piston provided a piston head arranged to move from top to bottom and inserting the at least one top plug into the orifice upper 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

20 arranged to bring the at least one upper plug into the insertion position at the piston head of the second piston In an advantageous embodiment according to the invention, the means for supplying a series of lower plugs are located in a lower closure zone and include a vibrating bowl arranged to contain a series of bottom plugs and positioning them in an insertion position, a first piston fitted with a piston head, arranged to move from bottom to the top and inserting the at least one lower plug into the orifice bottom 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

21 to bring the at least one lower plug into the position insertion to the piston head of the first piston.
Advantageously according to the invention, the filling means of the at least one lowerly sealed tube comprises a reservoir of sterile solution for injection and a filling needle connected to the reservoir of sterile solution for injection through a tube supply, the needle being arranged to discharge a quantity predetermined at a rate such that the predetermined quantity is discharged for a residence time T less than or equal to the time stay of the lowerly closed tube in the zone of filling, the filling needle being positioned above of the carousel plate.
In an advantageous embodiment of the device according to the invention, the supply means of a series of z tubes arranged to feed at least one tube of the series of z tubes into at least one carousel housing includes:
- A conveyor of tubs each comprising a nest in which tubes are placed through the holes in the nest, the conveyor being arranged to bring the tubs to a supply zone of nest, - A first robotic arm arranged to pick up a nest fitted with its tubes and place it on a centering table comprising a upper surface, the lower flanges of the tubes resting on the surface and part of the tubular wall of the tubes being exposed projecting through the openings of the nest when the nest is placed on the centering table, - A second robotic arm arranged to take at least one tube by gripping the exposed projecting tubes.

22 Advantageously according to the invention, the filling needle is sliding and has a high rest position and a low position filling, the fluid movement forming a filling curve.
Preferably, according to the invention, the supply means of at least a nozzle arranged to cause a nozzle to be associated with the at least one sealed and filled tube, comprises a third robotic arm, fitted with a forceps, arranged to remove each sealed and filled tube positioned in the collection area and convey it in a tub comprising a series from positions occupied by nozzles to the predetermined position of the tube on the nozzle to be assembled to form an assembled and filled container for needleless injection device.
In an advantageous embodiment of the invention, the means supply of at least one nozzle arranged to bring a nozzle to associated with the at least one sealed and filled tube comprises means for supplying at least one nozzle by a nozzle means provided with a head moving from bottom to top and whose head, fitted with the nozzle in low position moves vertically upwards to place the nozzle when the head is in the up position and form the assembled container and filled for a needleless injection device in a delivery area carousel nozzle, and returns to its low position without the nozzle, the medium nozzle being positioned under the carousel and where the collection means comprise a third robotic arm, fitted with a gripper, arranged to pick up an assembled and filled container and transport it to a tray.
Preferably, the device according to the invention comprises means for measuring the filling volume of each tube lowerly sealed and filled comprising a calibration unit and a high-precision unit of measurement.

23 Preferably, the lower sealing zone further comprises an inert gas injection zone allowing the elimination of oxygen. THE
inert gas is chosen from nitrogen, argon and/or the like. The injection of inert gas avoids any degradation of the solution which will be injected, to reduce the effect of oxidation and preserve the effectiveness of this solution. Another advantage is that the through tube further allows for more efficient purging for an inert gas.
Preferably, the filling further comprises an area injection of gas 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 is carbon dioxide. So particularly advantageous, a source of inert gas is connected directly to the filling needle allowing the injection of gas into any zone of the carousel, for example via a needle of dual-channel filling, in particular dual-channel filling concentric.
Preferably, the upper sealing zone comprises in addition to an inert gas injection zone allowing the elimination oxygen and protecting the solution by expelling carbon dioxide carbon. The inert gas is selected from nitrogen, argon and/or the like.
The injection of inert gas prevents any degradation of the solution which will be injected, to reduce the effect of oxidation and preserve the efficiency of this solution.
Advantageously, the upper sealing zone is coupled with a verification zone of the space created between the solution and the top cap by measuring the height between the top of the meniscus of the solution and the lower end of the upper stopper.
This verification zone further comprises control means

24 the positioning of the upper stopper, preferably the means of control 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 0.35mm.
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 emerge from the description given below, on a non-limiting basis and in referring to the drawings and examples.
Figure lA illustrates a tub fitted with its nest and a series of tubing.
Figure 1B illustrates a nest comprising a plurality of sterile containers.
Figure 2 is an overview of the assembly device and filling containers for a needleless injection device explaining the main steps of the present invention.
Figure 3 is a sectional view of the feeder carousel of empty tubes placed in a nest and moved by a first robotic arm.
Figure 4 is a sectional view of the tube sample vacuum by gripping using a gripper of a second robotic arm.
Figure 5 is a side view of the evacuation step of the empty tub after feeding the carousel by the first robotic arm.

Figure 6 is an overview of the capping steps, filling and cap feeding.
Figure 7 is a view of the tube collection stage filled and closed by a third robotic arm followed by assembly on 5 the nozzles in the tray and the conveying of the tray filled with tubes filled and assembled on nozzle.
Figure 8 is a detailed view of the vibrating bowl.
In the figures, identical or similar elements bear the same references.
10 The list of references used is described below:
1 - tube 1' - lower tube closed 1" - tube bottom capped and filled 1'" - tube capped and filled 15 2 - tubular wall 3 - upper hole 4- lower hole 5 - upper flange 6 - lower flange 20 7 - top cap 8 - bottom plug 9- nozzle 10- feed medium 10- second robotic arm

25 11 - conveyor or rail for bottom caps 11/13- bottom cap feed way 13- first plunger for inserting the bottom plug

26 12- conveyor or rail for top caps 12/14- way top cap feed 14- second plunger for inserting the top plug 15- medium filling 16 - nozzle feed means 18- collecting way 19 - lower plugging area 20 - filling area 21 - upper capping area 22 - rotating carousel 23- plate 24- housing 26 - means of rotation 28-tub 29 - nest 30- receiving hole 31 - allocation table 32- third robotic arm 33- motion system 34- centering table 37- clamp 38- feed tube 40 - container assembled and filled 41 - filling needle 42 - vibrating bowl 43- conveyor 44- sealing cap 44- means of maintenance

27 45- lid 46 - drug solution 47- tray 48- vibrating bowl 49 - conveyor 50 – first robotic arm (classically called a denetting arm) 51 - gripping means of the first robotic arm 52- gripper of the 2nd robotic arm 53 - motion system Detailed description of an embodiment of the invention Other features and benefits of this invention will become apparent from the non-limiting description which follows, and doing reference to drawings.
As mentioned above, the present invention relates to the field of transdermal injection devices without needle that give excellent results in terms of rapid distribution and uniform in the human body or in the animal body without actually require expertise or present a risk of poorly located injection.
These needleless injection devices inject under the skin the drug substance contained by a deflagration or under high pressure. The medicinal substance is contained in a sterile container. The sterile container is inserted into an injector needleless transdermal.
Figure lA illustrates a tub fitted with its nest 29 and a series of tubes 1.
The nest 29 is a support, often made of plastic, with holes for receiving 30 tubes. The nest is placed in a tub 28 sealed by a

28 closing cap 44 which makes it possible to obtain a barrier system sterile.
Each tube 1 comprises a tubular wall 2, an upper orifice 3, a lower orifice 4, an upper flange 5 extending peripherally of the tubular wall 2 around the upper orifice 3 and a lower collar 6 extending peripherally from the wall tube 2 around the lower orifice 4.
Figure 1B illustrates a nest 47 comprising a plurality of containers sterile, ready to be introduced into an injector actuator transdermal.
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 caps. A lower plug 8 is located in the orifice bottom 4 of tube 1. An upper plug 7 is located in the orifice upper 3 of tube 1. Between the two plugs is the solution drug 46. The tube 1 blocked on either side is positioned in a nozzle 9. The sterile containers provided with nozzles 9 are introduced into a tray 47 provided with a lid 45.
Figure 2 illustrates a device for assembling and filling containers for needleless injection device 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 supply 10 of a series of z tubes 1 arranged to supply the at least one tube 1 of said series of z tubes 1 in at least one housing 24 of said carousel 22. In the embodiment illustrated in Figure 2, THE
carousel includes 8 slots 24 that move as you go of the rotation for each move from position A to position B, the position C, position D, position E, position F, position G and finally the

29 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. 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 means supply 11, 13 of a series of lower caps 8. The means supply 11, 13 is located under the plate 23 of the carousel and is arranged to supply a lower plug 8 at least partially in 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 tube closed (1') by said lower plug 8.
The device according to the present invention further comprises a means of filling 15 of said at least one lower closed tube 1'. The way filling 1.5 is arranged above the plate 23 of the carousel 22 and arranged to pour said sterile formulation to be injected into said au at least one lower closed tube 1' to form at least one tube lowerly sealed and filled 1". The filling is carried out in the tube 1 which is in the housing 24 in position D. according to the shape of illustrated achievement. The device according to the present invention comprises besides an inert gas supply means, preferably connected to the filling medium.
The device also comprises a supply means 12,14 of a series of upper caps 7, which is located above said plate 23 of the carousel 22 and arranged for closing the upper orifice 3 of the lower tube sealed and filled 1" with at least one introduction partially of at least one stopper 7 of said series of stoppers upper 7 in the upper orifice 3 of said at least one tube bottom capped and filled 1" to form at least one capped tube and filled 1'".
The device also comprises a supply means 16 of at least 5 a nozzle 9 arranged to cause a nozzle 9 to be associated with said au least one closed and filled tube 1"' and a collection means 18 of said at least least one container 40 assembled and filled for an injection device without needle. In the embodiment illustrated in Figure 2, the means supply of at least one nozzle is a conveyor which brings a 10 tray 47. The tray 47 comprising a series of nozzles 9 is brought onto a centering table 31. The centering table 31 goes allow the nozzle 9 to be presented to the third robotic arm 32 in such a way that the third robotic arm 32 performs a single and unique movement. There distribution table 31 allows the centering of the tray 47 containing 15 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 housing in position G in the tray 47 on the table distribution 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 20 in this embodiment the tray comprising each nozzle 9 fitted with a sealed and filled 1" tube 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 up to position G of the 25 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 out of the tray before being replaced.
The tubs 28 are moved by a conveyor 43 to allow powering of the nest 29 in the device, plus particularly on the centering table 34. The nests 29 provided with the tubes 1 are placed (denested) on a centering table 34 by a first arm or robotic stripping arm 50. 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 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 trajectory of displacement passing through a lower blocking zone 19, 10 represented in the illustrated embodiment by position C, a fill area 20, shown in the illustrated embodiment by position D and an upper sealing zone 21, shown in the embodiment illustrated by position E. The caps lower 8 are fed below the carousel plate 22 in the lower sealing zone 19 by the combination of a conveyor 11 and a vibrating bowl 42. The upper plugs 7 are fed above of the carousel plate 22 in the upper sealing zone 21 by the combination of a conveyor 12 and a vibrating bowl 48. Between the zone of lower stopper 19 and the upper stopper zone 21, figure 2 illustrates the filling zone 20 which includes a filling means 15 provided with a filling needle 41. Once the tube is sealed and filled 1"', the tube l'" (in position G) is then conveyed on a tray 47 comprising the nozzles 9 by a third robotic arm 32.
The filling needle 41 can be a double channel needle, preferably a needle with concentric double channels allowing to inject inert gas into each area of the carousel.
Figure 3 is a sectional view of the feeder of the carousel of empty tubes arranged in a nest 29. The tubs 28 are moved by a conveyor 43 to allow feeding of the nests 29 in the device, more particularly on the centering table 34. The nests 29 fitted with tubes 1 are placed on a centering table 34 by a first robotic arm 50 rotating. The first robotic arm or arm of stripping comprises a gripping means 51 which grips the nest 29 and the deposited on the centering table 34 before releasing it (stripping).
Once placed on the centering table 34, the tubes 1 are exposed in protrude through the orifices of the nest 30 and rest on their flanges lower 6 allowing a second robotic arm 10 to take the tube 1 of 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. Depending on the shape of realization of the method, the gripping means for the robotic arms used is pliers, but of course it is possible to use any other means of gripping, such as for example 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 arm robotic 10, to be brought into a housing 24 of the carousel 22. The second robotic arm 10 includes a clamp 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 a top wall. The rotation of the carousel is permitted by means of rotation 26 around the axis of rotation R of the carousel plate 22 allowing the tube 1 to move consecutively from the feeding area to the area of lower capping 19, the filling area 20 and the capping area upper 21, bringing the tube positioned in position A, towards the position B, then to position C, etc, until position G where it is collected according to the illustrated embodiment.
In figure 6 the lower plugging is carried out in the lower plugging zone 19, or when the tube is in position C according to the embodiment illustrated by bringing a lower plug 8 to the means of a first piston 13 provided with a piston head moving from bottom upwards by means of a movement system 53. The piston head fitted with lower plug 8 moves upwards vertically to insert the lower plug 8 into the lower hole 4 of the tube 1 under the carousel 22 to form the bottom closed tube 1'. When the plug is inserted, the piston head returns to its position low without the lower stopper 8. During the positioning of the lower stopper bottom of the holding means 44 exert pressure on the part upper part of tube 1, in particular on the upper collar 5.
The feeding of the bottom caps 8 in the capping area lower 19 comprises a vibrating bowl 42, which orients the cork in the correct orientation (top of cap up and bottom of cap down) and the cork is conveyed in the correct position to the zone of lower plug 19. The polarity of the plug allows its installation in tube 1. The bottom plug feed 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 a zone injection of inert gas 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 orifice upper 3 of the lower closed tube 1'. Filling includes furthermore an inert gas injection zone allowing the elimination of oxygen and the activation of the solution. The amount of sterile formulation to be injected is predetermined and is discharged by means of a pump via a filling needle 41 which is located above the carousel 22 to form the lower capped and filled tube 1". The filling needle 41 is sliding and has a high rest position and a position filling bass. The filling needle 41 is positioned above above the meniscus of the sterile solution to be injected, i.e.
the filling needle 41 moves from bottom to top as it as the sterile solution to be injected is inserted into the tube inferiorly sealed 1'. The filling needle 41 is connected to a feed pipe 38 itself connected to a pump and fed by an intermediate reservoir of sterile solution for injection, not illustrated in the figures, to form the filling means 41.
The top plug 7 is introduced into the 1" tube in the zone upper stopper 21 by means of a second piston 14 provided with a piston head moving from top to bottom by means of a system movement 33. The piston head is fitted with the plug upper 7 and moves down vertically to introduce the top plug 7 in the tube 1" above the top meniscus of the sterile solution and from above the carousel 22 to form the tube closed and filled 1". When the stopper 7 is inserted, the piston head returns to its high position without the top cap 9. The supply of the top caps 9 in the top cap 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 plugging zone upper 21 further comprises an inert gas injection zone (not shown) allowing the elimination of oxygen and the protection of the solution by expelling carbon dioxide. The plugging area upper 21 is coupled to a verification area (not shown) of the space created between the solution and the upper stopper 9 by a measurement of the height between the top of the meniscus of the solution and the lower end of the top cap. This verification area further comprises means for controlling the positioning of the top cap 9, preferably the control means is a camera. The height between the top of the meniscus of the solution and the end lower part 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 0.35 mm.

The stages of lower capping, filling and upper capping are carried out consecutively by movement of the carousel.
Figure 5 is a side view of the evacuation step of the 5 tub 28 empty after feeding the carousel 22 by the first arm robotic 50. The tubs 28 are moved by a conveyor 43 to allow feeding 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 10 robotic arm or stripping arm comprises a gripping means 51 which seizes the nest 29 and places it on the centering table 34 before let go. 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 15 third robotic arm 32 provided with a gripper 37 allowing to move the tube closed and filled 1"' from the carousel 22 to a 2nd centering table 31 where there is a nest or a tray 47. The nest or the tray, shown after generically called tray 47 comprises a series of positions occupied by nozzles 9. The filled and closed tube 1" is 20 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 needleless injection device.
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 25 and unique movement. The distribution table 31 allows the centering of the tray 47 containing a nozzle 9 plumb with the third arm robotized 32. Once the tray 47 is filled with the containers assembled and filled, it is evacuated from the centering table 31 towards the conveyor 49.

In the embodiment illustrated in Figures 1 to 7, the number of slot 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 slot corresponds to position A and the eighth slot to position position H. Each position is spaced one-eighth of a turn from 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 slot in position A and the other slots are empty. THE
carousel 22 performs an eighth of a turn and the first housing in position A goes to position B. The eighth slot in position H goes in 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 goes to position E. The third housing in position C goes in position D. The second housing in position B moves to position C.
Then, the first housing in position B moves to position C, the zone of lower plugging, while the seventh housing in position H passes in 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 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 is then in position D. In sequence, the carousel performs another eighth of a turn and the first housing in position C changes to position D (filling area 20), the eighth slot in position B
moves to position C, the seventh slot in position A moves to position B, the sixth housing in position H goes to position A, the fifth housing in position G moves to position H, the fourth housing in position F goes to position G, the third housing in position E goes in position F, the second housing in position D moves 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 (3rd housing), or in the lower sealing position. The third tube is in position D (enie housing), i.e. in the filling position and the second tube is in position E (5th housing), i.e. in the plugging position superior. 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 housing, sixth housing and eighth slot) remain free.
It is understood that the present invention is in no way way limited to the embodiments described above and that many modifications can be made without departing from the scope of the appended claims.
For example, provision can be made to implement the method according to the present invention in a device comprising a clamp coming to grip a tube, said gripper performs a rotational movement between at least two positions. Advantageously, the tube is moved by a circular motion between a first position and a second place. The first position is intended for the introduction of the bottom cap and/or filling to obtain a tube lower sealed and/or filled. In another embodiment, the position of the insertion of the lower stopper is different from the position filling. The second position is intended for the introduction of the upper stopper to obtain a closed and filled tube.

Claims

38 1 .
Z assembly and filling process needleless injection device containers, each container including:
- a tube (1) comprising a tubular wall (2) defining an orifice upper (3) and a lower orifice (4), an upper collar (5) extending peripherally from the tubular wall (2) around the upper orifice (3) towards the outside and possibly a lower collar (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 orifice lower (4), 1 5 - 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, particular explosive discharge, the aseptic filling process comprising the steps of:
(i) a supply (10) of at least one tube of a series of z tubing (1) (ii) a supply (11) of a series of bottom caps (8) (iii) placement (13) of bottom plugs (8) during which at least one bottom plug (8) is inserted at least partially in said lower orifice (4) of a tube (1) of said series of tubes (1) to form at least one tube lowerly closed off (1') by said lower plug (8) (iv) a filling (15) of said at least one tube below sealed (1') by pouring said sterile formulation into injecting into said at least one lowerly sealed tube (1'), to form at least one bottom-closed tube and filled (1"), (v) a supply (12) of a series of top caps, (vi) a closure (14) of the upper orifice (3) of said tube lowerly sealed and filled (1") by an introduction to the at least partially of at least one stopper of said series upper plugs (7) in the upper orifice (3) of said at least one bottom sealed and filled tube (1") for form at least one sealed and filled tube (1"'), (vii) a supply (16) to a series of nozzles (9), (viii) placement of said at least one sealed and filled tube (1"') in at least one nozzle (9) of said series of nozzles, to form at least one assembled and filled container for needleless injection device, and (ix) collection (18) said at least one assembled container and filled for injection device, said steps (iii), (iv), (vi) being carried out consecutively by at least one displacement of said at least one tube (1) according to a trajectory of movement passing through a clogging zone bottom (19), and/or a filling zone (20) and a upper plug (21), said displacement of said at least one tube (1) being performed by rotation, for example of at least one carousel rotary (22) comprising a plate (23) provided with a series of housings (24) each provided with at least one through hole (25) and of an upper wall, said at least one powered tube (1) being disposed in a housing (24), said rotation of said carousel (22) being arranged to confer on said at least one tube (1) said movement along the aforesaid movement trajectory.
2. Process according to claim 1, wherein said supply (10) of a series of tube (1) is carried out according to the steps of a) Feeding a conveyor by means of tubs (28) each comprising a nest (29) in which tubes (1) are arranged through the orifices (30) of the nest (29), b) A sampling of the nest (29) equipped with these tubes (1) by a first robotic arm (50), during which the flanges upper parts (5) of the tubes (1) rest on a surface top 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 sample of at least one tube by gripping the means of a gripper positioned on a second arm robotized (10), a movement of the tube (1) by placing movement of the robotic arm (10) and placement of said tube (1) in a housing (24) of said carousel (22).
3. Process according to claim 1, wherein each zones chosen from the supply zone, the plugging zone lower (19), the filling area (20), the upper capping area (21) and the collection area, is occupied by a housing of said series 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 another.

4. Process according to claim 3, wherein the number of slots in the series of slots (24) is equal to or greater than to 2, preferably equal to or greater than 3, preferably equal to or greater to 4, preferably equal to or greater than 5 corresponding to the number of minimum areas.
5. Method according to claim 3, in which the number of slots in the series of slots (24) is greater than 5 and wherein a housing of said series of housings is positioned between two zones selected from the supply zone, the plugging zone lower (19), the filling area (20), the upper capping area (21) and the collection zone, equipped or not with a tube.
6. Method according to any one of the claims above, in which each tube closed, filled and positioned (1"') in the collection area is collected by means of a third arm 1 5 robotic (32), provided with gripping means, and is conveyed by the third robotic arm (32) in 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 a container assembled and filled for needleless injection device.
7. Process according to claim 6, in which the tray (47) comprising the assembled and filled containers for needleless injection device is placed in a tub (28) by a means movement, for example by a fourth robotic arm or a conveyor (49).
8. Method according to one any of claims 2 to 7, in which each tube closed and filled (1'") then positioned in a nozzle laying area where a nozzle (9) is associated with said tube closed and filled (1"') by bringing a nozzle (9) through a means of nozzle provided with a head moving from bottom to top and whose head, equipped with the nozzle (9) in the low position moves vertically towards the high to place the nozzle (9) when the head is in the high position and form said assembled and filled container (40) for an injection device without needle, and returns to its low position without the nozzle (9), said means of nozzle being positioned under the carousel (22).
9. Method according to one any of the claims previous ones, 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 bottom to top and whose piston head, fitted with the stopper in the lower position moves vertically upwards in the lower orifice (25) of said housing (24) of the tube (1) to place the lower cap (8) when the head is in the high position and form said lowerly sealed tube (1'), and returns to its low position without said lower plug (8), said first piston (13) being positioned under the carousel (22).
1 O.
Method according to any one of the claims above, wherein the filling of said at least one tube lowerly closed (1 ') is carried out by pouring said sterile formulation to be injected into said at least one tube below closed (1') by means of a filling needle (41) arranged to discharge a predetermined quantity at a rate such that the quantity predetermined is discharged for a smaller residence time T or equal to the residence time of the lower closed tube (1') in the zone filler (20), to form said at least one tube below closed and filled (1"), said filling needle (41) being positioned above the carousel (22).
11.
A method according to claim 10, wherein said filling needle (41) is sliding and has a high position rest and a low filling position.

12. Method according to any one of the claims previous ones, in which the upper capping 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 cap (7) in the high position moves vertically towards the low in the upper orifice (3) of the lower tube closed and filled (1"), to place the upper cap (7) there when the head is in position low and form said sealed and filled tube (1'"), and returns to its position high without said upper plug (7), said second piston (14) being positioned above said carousel (22).
13. Method according to any one of the claims previous steps, in which the steps are carried out in a manner consecutive by continuous movement of the plate (23) of said carousel (22).
14. Method according to any one of the claims previous steps, in which the steps are carried out in a manner consecutive by discontinuous movement of the plate (23) of said carousel (22).
15. Z assembly and filling device needleless injection device containers, each container including:
- a tube (1) comprising a tubular wall (2) defining an orifice upper (3) and a lower orifice (4), an upper collar (5) extending peripherally from the tubular wall (2) around the upper orifice (3) towards the outside and possibly a lower collar (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 orifice lower (4), - a nozzle (9) arranged to house said tube (1), said containers being arranged to then be, once assembled and filled of a sterile formulation to be injected, introduced into an actuator self-injection, in particular explosive discharge, said device being composed of:
- a rotary carousel (22) comprising a plate (23) provided of a series of housings (24) each provided with at least one orifice crossing (25), - means for rotating said plate (23) arranged to impart rotation to the plate (23) about an axis of rotation, - a supply means (10) of a series of z tubes (1) arranged to supply at least one tube (1) of said series of z tubes (1) in at least one housing (24) of said carousel (22), - a supply means (11) of a series of lower plugs (8), located under said plate (23) and arranged to supply a lower plug (8) at least partially in the lower hole (4) of a tube (1) of said series of tubes (1) to form at least a lower tube closed (1 ') by said lower plug (8), - a filling means (15) of said at least one tube lowerly sealed (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 minus one bottom sealed and filled tube (1"), - a supply means (14) of a series of upper plugs (7), located above said plate (23) and arranged to the closing of the upper orifice (3) of said tube below closed and filled (1") by an introduction at least partially at least one plug of said series of top plugs (7) in the upper orifice (3) of said at least one tube below capped and filled (1") to form at least one capped and filled tube (1, , ,), - a supply means (16) of at least one nozzle (9) arranged 5 for causing a nozzle (9) to be associated with said at least one tube sealed and filled (1"'), and - a collection means (18) of said at least one assembled container and filled for injection device (40).
16. Device according to claim 15, wherein said 10 average supply (12) of a series of upper plugs (7) is located in an upper sealing zone (21) and comprises a vibrating bowl (48) arranged to contain a series of top plugs (7) and the position in an insertion position, a second piston (14) provided a piston head arranged to move from top to bottom and inserting said at least one upper plug (7) into 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 cap upper (7) in the position of insertion to said piston head of said 20 second plunger (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 capping area (19) and include a bowl vibrator (42) arranged to contain a series of lower plugs (8) and 25 the positioning in an insertion position, a first piston (13) provided a piston head, arranged to move from bottom to top and inserting said at least one lower plug (8) into 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 insertion position at said piston head of said first piston (13).
18.
Device according to one of Claims 15 to 17, in wherein the filling means (15) of said at least one tube lowerly sealed (1') comprises a reservoir of sterile solution 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 amount is discharged for a time residence time T less than or equal to the residence time of the sealed tube below (1') in the filling zone (20), said needle of filling (41) being positioned above the plate (23) of the carousel (22).
19.
Device according to one of Claims 15 to 18, in wherein the supply means (10) of a series of z tubes arranged to feeding at least one tube (1) of said series of z tubes into at least a housing (24) of said carousel (22) comprises:
- A conveyor (43) of tubs (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 area (34), - A first robotic arm (50) arranged to pick up a nest (29) equipped with its tubes (1) and place it on a centering table (34) comprising an upper surface, the lower flanges (6) tubes (1) resting on said surface and part of the wall tubular (2) of the tubes being exposed projecting through the orifices of the nest (30) when the nest (29) is placed on said table of centering (34), - A second robotic arm (10) arranged to pick up at least one tube (1) by gripping the projecting exposed tubes.

20. Device according to claim 18 or claim 19, wherein said filling needle (41) is slidable and has a high position of rest and a low position of filling.
21. Device according to one any of the claims 16 to 20, wherein said supply means (16) of at least one nozzle (9) arranged to cause a nozzle (9) to be associated with said at least one tube closed and filled (1'"), comprises a third robotic arm (32), equipped a clamp, arranged to remove each sealed and filled tube (1"') positioned in the collection area and transport it in 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 for form an assembled and filled container for an injection device without needle (40).
22. Device according to one any of the claims 15 to 21, wherein said supply means (16) of at least one nozzle (9) arranged to cause a nozzle (9) to be associated with said at least one tube closed and filled (1'") comprises supply means (16) of at least at least one nozzle (9) by a nozzle means provided with a head moving from bottom to top and whose head, provided with the nozzle (9) in low position moves vertically upwards to place the nozzle (9) when the head is in the up position and form said container assembled and filled for a needleless injection device (40) in a nozzle laying area 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 collection means (18) comprises a third arm robotic (32), fitted with a gripper, arranged to pick up a container assembled and filled (1"') and convey it in a tray (47).