FR3036963A1 - PROCESS FOR MANUFACTURING PRE-FILLED SYRINGES WITH NEEDLE ADHESIVE - Google Patents

Abstract

The invention relates to a method for manufacturing pre-filled syringes with a bonded needle, comprising the steps of mounting a device (D) for protecting the needle on syringe bodies (2), the device comprising an outer sleeve, which is movable along a longitudinal axis between an advanced position, where it covers the needle, and a retracted position, where it does not cover the needle, return means of the sleeve in the advanced position and a needle guard disposing the syringe bodies (2), equipped with the protective device, in housings (0204) provided in a support (200), placing the support (200) in a container (100) for transport, exiting supporting the container, filling each syringe body with an active ingredient, inserting a plunger into each syringe, and removing the syringes (1) from their support for inspection and labeling.

Description

The invention relates to a method for manufacturing pre-filled syringes with a glued needle.

In known manner, some syringes are equipped with an after-use safety system, whose function is to protect the needle of the syringe at the end of the injection. This avoids injury with the needle when it is removed from the body of the patient and helps fight against the transmission of diseases, such as HIV. Currently, pre-filled syringes with glued needle are manufactured in the following manner: The glassmaker assembles a flexible or rigid needle guard at the end of each syringe body with glued needle. The syringe bodies, then each equipped with a needle guard, are then placed in a plastic support, called "rack". This rack is in fact a plate delimiting a series of holes for receiving the syringe bodies. The racks are then placed in transport containers, which are sealed with a film of synthetic material. The containers are sterilized with ethylene oxide, which is able to pass through the lid. When the containers are received by the pharmaceutical laboratory, they are opened in a sterile environment and the racks are taken out and placed on automatic filling machines. Each syringe body is then filled with an active ingredient, and a plunger, also called a "piston seal," is pushed into each syringe body. The syringe bodies are then taken out of the racks to place them on an inspection and labeling line. Once this is done, the syringe bodies are moved to another assembly line to incorporate the safety system and a piston push rod, which is able to activate the safety system once the injection is completed. completed. The major drawback of this method is that it is necessary to invest in bulky and expensive infrastructure to provide the syringes with a security system after use. Another disadvantage is that the selected security system is particularly bulky, so that the syringes can not be packaged with standard blister packaging or standard secondary packaging (cardboard box). In particular, the final packaging is particularly bulky, which leads to a high transport cost. Finally, the piston push rod used is not standard since it has washers to activate the safety system after the injection is complete.

It is these drawbacks that the invention intends to remedy more particularly by proposing a method for manufacturing pre-filled syringes that can be implemented with a less bulky and less expensive installation. To this end, the invention relates to a method of manufacturing pre-filled needle syringes, which comprises the steps of: a) mounting a needle protection device on syringe bodies, the device comprising a system after use and a needle guard, b) arrange the syringe bodies, equipped with the protection device, in 10 housings provided in a standard support, c) place the support in a standard container, close the container and sterilize the container. container for transport and, d) in a sterile environment, take the carrier out of the container, e) fill each syringe body with an active ingredient, f) insert a plunger into each syringe, g) remove the syringes from their holder for inspection, piston rod assembly and labeling; and (h) individually pack each syringe with primary packaging and secondary packaging.

With this method, the needle protection device can be set up directly by the glassmaker, that is to say at the same time as the needle guard, because the latter is integrated in the device. The pharmaceutical companies do not need to provide an assembly line dedicated to mounting the safety system after filling. This saves space in the syringe assembly infrastructure. In addition, the protective device incorporating the needle guard is sufficiently compact, so that the syringes can be arranged, in step b), with their protective device in a holder, or "rack" standard. Similarly, standard piston rods can be used. The final packaging is also standard and compact. Thus, the existing industrial manufacturing process is not disturbed, but on the contrary simplified. According to advantageous but non-obligatory aspects of the invention, the manufacturing method may incorporate one or more of the following features, taken in any technically permissible combination: Step a) is carried out by a glass maker producing the syringe bodies. 3036963 3 - The syringes do not touch the bottom of the container when the support is placed in the container, that is to say in step c). The device mounted on each syringe body has at its distal end an annular chamfer so that, in steps b) and g), the insertion and extraction of the devices in and out of the housing of the support is effected. without snags. - In step g), the piston rod is screwed on the piston. - The primary packaging used in step g) is a transparent shell packaging. - The secondary packaging used in step g) is a cardboard box. Each device comprises elastic fixing means on a corresponding syringe body. - The attachment means include resilient tabs adapted to cooperate with the end portion, the end portion being shaped to block the release of the tabs once the device mounted. Steps d) to f) are automated.

The invention and other advantages thereof will appear more clearly in the light of the following description of an embodiment of a manufacturing method according to its principle, made solely by way of example and with reference to the accompanying drawings in which: - Figures 1, 3, 5, 7, 9, 11 and 13 each show a side view of a glued needle syringe, comprising a needle protection device; Figures 2, 4, 6, 8, 10, 12 and 14 each represent a longitudinal section, on a larger scale, of the syringe corresponding to the figures mentioned above, - Figures 15 and 16 are longitudinal sections and at most large scale, of the device for protecting the syringe of FIGS. 1 to 14, in two different section planes, FIGS. 17 to 21 are longitudinal sections showing steps of assembling the device of FIGS. 1 to 16 on a syringe with glued needle, - FIG. 22 is a perspective view showing a transport container for manufacturing syringes with glued needles as shown in FIG. 1; FIG. 23 is a section along the plane XXIII of FIG. 22; FIG. is an enlarged view of the circled XXIV of FIG. 23, and - FIGS. 25 to 27 are perspective views each representing a step of the manufacturing method according to the invention.

In each of Figures 1 to 14 there is shown a syringe with glued needle 1. This syringe 1 is pre-filled type and extends along a longitudinal axis X1. It comprises a syringe body 2, generally made of glass, which is generally tubular and centered on the axis X1. The body 2 has a nose 8 into which is dug a hollow needle 10. The needle 10 is fixed inside the nose 8 by gluing. The nose 8 has an external recess 80. The needle 10 has a distal end 10.1 bevelled. The syringe body 2 contains an active ingredient P, such as a drug. The syringe 1 also comprises a standard rod 4 which is equipped at its end with a seal 6. The seal 6 serves as a piston for ejecting the active ingredient P through the hollow needle 10, which is why the seal 6 is commonly called "piston" or "piston seal". The seal 6 is attached to the rod 4, that is to say that it is linked in translation with the rod 4 in both directions of displacement. More specifically, the rod 4 is screwed inside the seal 6. At the opposite of the seal 6 along the axis X1, the rod 4 is equipped with a pallet 42 on which the user can exert a thrust force to the nose 8. The rod 4 is displaceable in translation relative to the body 2 along the axis X1, that is to say that it is able to slide inside the syringe body 2. In this description, the forward or distal direction means a direction parallel to the longitudinal axis X1 and facing the epidermis of the patient under normal conditions of use of the syringe 1, while the rear or proximal direction is oriented to 20 opposite to the injection zone, the side of the pallet 42. The syringe 1 comprises, at the front, a device D for protecting the needle 10. This device D is adapted to be mounted on the end before the syringe body. The device D incorporates a needle guard 12 which makes it possible, on the one hand, to keep the needle clean prior to the use of the syringe 1 and thus to avoid the pollution of the active ingredient P, and on the other hand to protect the needle 10 against any external mechanical action. For example, the needle guard 12 prevents the needle 10 from bending or breaking before use. The needle guard 12 is a rigid needle guard comprising a flexible tip 14 into which the needle 10 is inserted and a rigid sheath 16 which surrounds the tip 14.

The tip 14 is elastomer (rubber) or injectable thermoplastic material, while the rigid sheath 16 is plastic, in the example high density polyethylene (HDPE). The needle guard 12 is better visible in FIGS. 15 and 16. As can be seen in these figures, the tip 14 comprises, at the front, a narrowed section 142 forming an annular shoulder 140 which widens the diameter of the tip 14 by going forward. The tip 14 also has, at the rear, a skirt 144 surrounding a portion 3036963 5 of the needle 10. The tip 14 is compressed against the nose 8 of the syringe body 2. The skirt 144 is frustoconical and s' widens towards the rear of the tip 14. The rigid sheath 16 is in two parts 16a and 16b which are detachable from each other by a relative rotational movement between the two parts 16a and 16b. Indeed, the two parts of the sheath 16a and 16b are interconnected by breakable bridges 162, designed to be broken when applying a moment M1 relative rotation between the two parts of the sheath 16a and 16b . Part 16a is disposed at the front of part 16b. The parts 16a and 16b are each tubular in shape centered on the longitudinal axis X1.

The rear part 16b of the sheath 16 is snapped around the nose 8 of the syringe 1, that is to say it comprises elastic fixing means around the nose 8 of the syringe 1. These fixing means comprise resilient tabs 166 which are shaped to become wedged in the recess 80 of the nose 8. The portion 16b is therefore rotationally integral with the syringe body 2. The rear portion 16b of the rigid sheath 15 also has two diametrically opposite pins 160 , which protrude radially outwardly relative to the longitudinal axis X1. Only one of these pieces is however visible in the figures. The device D comprises translational linking means, along the axis X1, between the endpiece 14 and the portion 16a of the sheath 16. These connecting means comprise teeth 164 formed on an internal radial surface of the front portion 16a of the sheath. These teeth 164 protrude radially from the longitudinal axis X1 towards the inside of the sheath and cooperate with the annular flange 140 of the endpiece 14, so that the endpiece 10 is linked in translation with the front part 16a. However, a rotation of the sheath 16 about its axis does not cause rotation of the end-piece 14, that is to say that the sheath 16 and the end-piece 14 are not secured to each other. in rotation around the longitudinal axis X1. The front portion 16a of the sheath 16 has at its front end a central pin 168 extending axially rearwardly. There is an axial clearance J2 of about 1 mm between the pin 168 and a front end surface S14 of the tip 14. The clearance J2 is measured parallel to the axis X1. On the other hand, there is clearance between the outer surface of the tip 14 and the inner surface of the sleeve 16. This clearance is measured in a direction normal to the outer surface of the tip 14, which is slightly oblique by relative to the X1 axis. Thus, the tip 14 is not likely to rotate integrally with the front portion 16a of the sheath 16 by friction. Protective device D also includes a safety system to protect needle 10 after use of syringe 1, i.e., when syringe 1 is removed from the patient's body. This system comprises an outer sleeve 18, which is arranged coaxially around the rigid sheath 16. The sleeve 18 is made of opaque material, to completely hide the needle 10. This sleeve 18 defines an internal radial flange 182 at its end. before and two recesses 180 in which the pins 160 are respectively inserted. In the example, the pins 160 do not protrude from the recesses 160 to the outside. The recesses 180 serve as a guide for the pins 160. Each recess 180 is generally asymmetric Y-shaped, with the Y branches extending rearwardly. The branches of the Y are referenced 180a and 180c, while its central portion is referenced 180b. This central portion 180b is a straight portion, i.e. a corridor. The device D also comprises locking means of the sleeve 18 in the advanced position, which are activated at the end of the injection. In the example, these locking means are formed by a housing 180d which extends from the branch 180c, forwards. The outer sleeve 18 is axially movable, i.e., along the axis X1, between an advanced position, where it covers the needle 10 and a retracted position, where the needle 10 is uncovered. The security system comprises elastic return means of the outer sleeve 18 in the advanced position. These return means comprise a helical spring 20 which is interposed between the internal radial flange 182 of the sleeve 18 and a shoulder 165 formed on the rear portion 16b of the rigid sheath 16. The coil spring 20 has a right-hand pitch, c ' that is, the winding direction of the spring 20 is on the right. This means that the spring 20 is wound on the right, or clockwise, when looking at the spring 20 from the bottom in Figures 1 to 14, that is to say the rear side. There is a radial mechanical clearance between the outer sleeve 18 and the rigid sheath 16, so that the sleeve 18 can slide around the sheath 16 without friction. However, there is no or little radial mechanical clearance between the sleeve 18 and the outer surface of the syringe body 2, so that the device D is not very bulky radially. In particular, the thickness of the sleeve 18 is chosen so that the syringes 1 can be inserted into the holes of a standard support.

Furthermore, the sleeve 18 has at its distal end an annular chamfer 18.1 which converges with respect to a central axis of the sleeve 18 towards the front and which is connected to the internal radial flange 182 by a peripheral fillet 18.2. described various steps of use of the syringe 1 with reference to Figures 1 to 14. First, the user must remove the rigid needle guard 12 to be able to perform the injection. To do this, he applies the moment M1 around the axis X1, as 3036963 7 shown in Figure 2, to turn the front portion 16a relative to the rear portion 16b and break the jumpers 162. Once the jumpers 162 broken , the user can remove the front portion 16a of the rigid sheath 16, as represented by the arrow F1 in Figure 2. The removal of the portion 16a integrally causes the removal of the tip 14 by the cooperation of the teeth 164 with the annular flange 140 of the tip 14. Thus, the tip 14 and the front portion 16a of the sheath 16 are removed from the syringe 1 without rotating the tip 14 around the needle 10, so that the end distal 10.1 of the needle 10, bevelled, does not form chips of material likely to penetrate the needle 10. The removal of the tip 14 and the front portion 16a of the sheath 16 brings the syringe 1 in the configuration of FIGS. 3 and 4. In this configuration, the needle 10 is completely covered by the sleeve 18. As the syringe 1 has not been used, the pins 160 of the rear portion 16b of the sheath 16 are housed in the branch 180a of the recesses 180. Referring to Figures 5 and 6, when the syringe 1 is brought against the epidermis of a patient, the pressure exerted by the sleeve 18 on the skin causes the recoil of the sleeve 18, as represented by the arrows F2 in FIG. 6. The spring 20 is then compressed, the needle 10 enters the epidermis and the pins 160 move from the branch 180a to the central portion 180b. The sleeve 18 moves back around the syringe body 2. Thus, the needle 10 is not discovered until the syringe 1 is brought against the epidermis of the patient, unlike the materials according to WO-A-1. 2013/134465 and WO-A-2007/077463, where the needle is partially uncovered before the syringe is brought against the body of the patient. In other words, the sleeve 18 is not moved back before the injection to reveal the needle 10. Thus, there is no risk of accidental puncture before injection. Continued movement brings the outer sleeve 18 to its retracted position, in which it no longer covers the needle 10. Continued movement occurs until the pins 160 arrive at the bottom of the passage 180b of the recesses 180 , as shown in FIGS. 7 and 8. In the configuration of FIGS. 7 and 8, the needle 10 of the syringe 1 is completely sunk into the epidermis of the patient. The user can then press the paddle 42 of the rod 4 to eject the active ingredient P contained inside the syringe 1 in the patient's body, as represented by the arrow F4 in FIG. The user withdraws the syringe 1 from the patient's body, the outer sleeve 18 is resiliently returned to the advanced position by the spring 20, as represented by the arrows F3 in FIG. 10. The outer sleeve 18 then returns to overlap the needle 10 and the pins 160 slide in the passage 180b of the recesses 180 in the direction of the branch 180c. The syringe 1 is then in the configuration of FIGS. 11 and 12, which corresponds to an end-of-injection configuration. If, after use of the syringe 1, an awkward user presses on the sleeve 18, that is to say tries to move back the sleeve 18, the pins 160 then move in the housing 180d of the recesses 180 and the displacement of the sleeve 18 to the rear is blocked, as shown in Figures 13 and 14. This is an additional security since the needle 10 can not be discovered at the end of injection. More specifically, the movement of the pins 160 of the branch 180c towards the housing 180d is favored because the spring 20 has a winding direction to the right. Indeed, this spring 20 10 exerts, when compressed, a torque on the sleeve 18 which is directed, because of its winding direction, in the counterclockwise direction in plan view in FIG. that is to say when looking at the syringe 1 on the side of the needle 10. This pair makes it possible to prevent the pins 160 from returning towards the corridor 160b if the user tries to move back the sleeve 18 after the injection . This torque also makes it possible to correctly guide the pins 160 in the passage 180b to the branch 180c of the recesses 180. FIGS. 17 to 21 show the steps for mounting the protection device D on the nose 8 of the syringe body. 2. A first step of mounting the protection device D is to bring the device D closer to the nose 8, as represented by the arrow F5 in FIG. 17. By continuing the approach movement in the direction of the arrow F5 the tabs elastics 166 are then deformed in a centrifugal radial direction F6 in contact with the nose 8, as can be seen in FIG. 18. Once the lugs 166 have passed the recess 80 of the nose 8, they snap against the latter by elastic return. of the material, as represented by the arrows F7 in Figure 19. The nose 8 of the syringe 1 is shaped to block the release of the tabs 166. There is a clearance J1 of about 1.5 mm between the extruder. emitted free of the legs 166 and the syringe body 2. The game J1 is measured parallel to the axis X1. In a last step illustrated in FIGS. 19 to 21, the needle guard 12 is pressed in such a way as to push the needle 10 well inside the endpiece 14. As can be seen in FIG. The tip 14 is then compressed axially between the lug 168 of the rigid sheath 16 and the nose 8 of the syringe body 2 and the clearance J1 between the free end of the lugs 166 and the syringe body 2 is caught. When releasing the pressure on the needle guard 12, the material of the tip 14 returns to its original shape and pushes the sheath 16 forward. The sheath 16 then returns to the latching position and an axial clearance J2 exists between the front end surface S14 of the endpiece 14 and the lug 168.

Below is described, with reference to FIGS. 22 to 27, a method of manufacturing pre-filled syringes with a glued needle 1, as previously described. In this document, a part is considered "standard" if it is already on the market, ie if it is already used in existing manufacturing processes. The method comprises a first step consisting of mounting a protection device D on each syringe with glued needle 1. This first step is performed by a glassmaker who manufactures the syringe bodies 2. As the protection device D incorporates the needle guard 12, the security system and the needle guard 12 are integrally mounted on the syringe body 2. This simplifies the existing assembly process. In addition, thanks to the elastic attachment means, the mounting of the device D on a syringe body 2 is simply by bringing the two elements together. A second step is to dispose the syringes 1, each equipped with a protection device D, in 0204 housings provided in a standard support 200. This support 200 is commonly called "rack" and consists of a rectangular plastic plate , which is holed. The holes 0204 of the plate 200 form the receiving receptacles of the syringes 1. These 0204 holes are standard in diameter of 9.3 mm. An outer casing surface of the device D has an outside diameter which is therefore less than 9.3 mm, in the example of the order of 9 mm. The holes 0204 are delimited by posts 204 which protrude upwards perpendicularly to the plate 200. The support 200 delimits sixteen rows of ten holes 0204. Thanks to the presence of chamfer 18.1 and leave 18.2 provided at its distal end, each device D is inserted without a hitch in a housing 0204 of the support 200. The body 2 of each syringe has, at an end opposite the nose 8, an annular shoulder 2.1 provided to abut against the free end of a column 204 , so as to prevent the syringe body 2 from falling under the effect of gravity. The plate 200 has two handles 202 facilitating its grip. When all the syringes are disposed in the rack 200, the latter is positioned inside a standard container 100. The container 100 comprises for this purpose two opposite shoulders 104, which each extend over the entire one side of the container 100. As shown in Figures 23 and 24, the syringes 1 do not touch the bottom 102 of the container 100 when the rack 200 is placed in the container 100.

The container 100 is then sealingly sealed by a film of synthetic material not shown, which is not gas-tight. The container 100 is rendered sterile by injection of gas, especially ethylene oxide. The ethylene oxide penetrates through the lid of the container, which makes it possible to sterilize the syringes inside the container. The containers 100 are then sent by the glassmaker to the pharmaceutical laboratory. As can be seen in FIG. 25, the containers 100 are opened in the pharmaceutical laboratory in a sterile environment and the racks 200 are automatically removed from the containers 100. The racks 200 are placed on automatic filling machines that are not shown to fill the containers. the syringe bodies 2 with an active ingredient P, as a drug. As shown in Figure 26, the filling machine comprises a row of ten filling tubes T, each adapted to be inserted into a syringe body 2. The active ingredient is then injected through the tubes T. Once all syringe body of one row are filled, the tubes T 15 are out of the body 2 and the support 200 is moved to fill another row of syringes. Once all the syringes 1 have been filled, a piston, or piston seal 6, is inserted inside each syringe body 2. As can be seen in FIG. 27, the bodies 2 of the syringes 1, then filled with active ingredient, are Out of the racks 200. The extraction of the syringes out of the support 200 takes place smoothly due to the presence of the annular chamfer 18.1 and the leave 18.2 on each device D. The syringes 1 are then placed on a line for inspection , the assembly of the piston rod 4 and the labeling. Specifically, the shaft 4 is screwed into the seal 6. The pre-filled syringes 1 are then individually wrapped with a primary package 300 and a secondary package 400. The primary package 300 is a standard clear shell package, better known as the name of "blister". The secondary packaging 400 is a standard cardboard box. The packaged product is compact and therefore easily transportable. These packages are shown, respectively in dashed lines and solid lines in Figure 1 only.

With this new method, the syringes 1 are delivered to the pharmaceutical laboratory with their integrated protection device D, so that the pharmaceutical laboratory does not have to assemble the protection device on each syringe. The pharmaceutical laboratory therefore does not need to have an assembly line dedicated to mounting the protective devices on the syringes, which saves space. In addition, the protection device D is very compact, so that the syringe 1 can be disposed in a hole of the rack directly with the protection device. In variant not shown, other return means that a spring can be envisaged to return the outer sleeve 18 in the advanced position at the end of injection. In variant not shown, a single recess 180 is formed in the sleeve 18. Similarly, the sleeve may define a number of recesses 180 strictly greater than two, for example equal to three. Alternatively not shown, the parts 16a and 16b of the sheath 16 can be screwed to each other or linked by a rotary locking mechanism. For example, the mechanism may comprise a pin guided in a curvilinear or bent groove. This type of mechanism is commonly referred to as a bayonet lock mechanism. In all cases, the parts 16a and 16b are detachable from each other by a relative rotational movement between the two parts.

As a variant not shown, the piston seal 6 is not attached to the rod 4, that is to say that the rod 4 is in simple support against the seal 6. The seal 6 is then linked to the rod 4 only in a direction of movement. According to another variant not shown, the container 100 defines an opening or a transparent portion for viewing the syringes 1 from outside.

The features of the variants and embodiments contemplated above may be combined with one another to generate new embodiments of the invention.

Claims (9)

CLAIMS 1. A method for manufacturing pre-filled syringes with a glued needle, characterized in that it comprises the steps of: a) mounting a device (D) for protecting the needle on syringe bodies (2), the device comprises a safety system after use (18, 20) and a needle guard (12), b) arranging the syringe bodies (2), equipped with the protection device, in housings (0204) provided in a support standard (200), c) place the support (200) in a standard container (100), close the container and sterilize the container for transport, d) in a sterile environment, remove the support from the container, e) fill each body syringe with active ingredient (P), f) insert a plunger (6) into each syringe, g) remove the syringes (1) from their support for inspection, assembly of a plunger rod (4) standard and labeling, and (h) individually pack each syringe (1) with a primary packaging (300) and a secondary package (400). 2. A process according to claim 1, characterized in that, in step c), the support (200) is placed in the container (100) so that the syringes (1) do not touch the bottom (102) container (100). 3.- Method according to one of the preceding claims, characterized in that the device (D) mounted on each syringe body has at its distal end an annular chamfer (18.1) which cooperates smoothly with a corresponding housing (0204) of the support in steps b) and g). 4.- Method according to one of the preceding claims, characterized in that, in step g), the piston rod (4) is screwed on the piston (6). 5.- Method according to one of the preceding claims, characterized in that the primary packaging used in step g) is a transparent shell packaging (300). 3036963 13 6. A method according to one of the preceding claims, characterized in that the secondary packaging used in step g) is a cardboard box (400). 7. Method according to one of the preceding claims, characterized in that each device comprises means (166) for resilient fixation on a corresponding syringe body, which are fixed, in step a), by approximation with the syringe body. 8. A method according to claim 7, characterized in that the fastening means 10 include elastic tabs (166) which cooperate, in step a), with an end portion (8) of the syringe body, this end portion being shaped to block the release of the tabs once the device (D) mounted. 9. A method according to one of the preceding claims, characterized in that the steps d) to f) are automated.