EP4719540A1 - Stoppering tool system for installing a valved stopper in a syringe barrel - Google Patents

Abstract

Provided herein is a vent tube stoppering system for positioning a stopper within a syringe barrel. The system includes a vent tube insertable into a chamber of the syringe barrel and having an internal volume configured to contain the stopper in a compressed state. The system also includes an installation rod moveable inside the internal volume of the vent tube so that installation rod may be operable to push the stopper distally out of the vent tube and into the syringe barrel. A distal end of the installation rob includes a shoulder portion and a tip portion extending out distally from the shoulder portion. When pushing the stopper distally out of the vent tube, the tip portion engages a bottom surface of a cavity in the stopper to apply a first pressure thereto, and the shoulder portion engages a proximal face of the stopper to apply a second pressure thereto.

Description

STOPPERING TOOL SYSTEM FOR INSTALLING A VALVED STOPPER IN A

SYRINGE BARREL

CROSS-REFERENCE TO RELATED APPLICATION

[0001] The present application claims priority to United States Provisional Application No. 63/468,668 entitled “Stoppering Tool System for Installing a Valved Stopper in a Syringe Barrel” filed May 24, 2023, the disclosure of which is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

Field of the Invention

[0002] The present disclosure relates generally to a stoppering tool system for installing a stopper in a syringe and, more particularly, to a stoppering tool system for installing a valved stopper in a syringe barrel.

Description of Related Art

[0003] Prefilled injection devices are common containers used to administer liquids (e.g., medications or drugs) to a patient and include syringes, cartridges and auto-injectors or the like. They usually comprise a plunger stopper in gliding engagement within a container, the container being filled with a pharmaceutical composition in order to provide the practitioners with a ready-to-use injection device for patients.

[0004] A container has a substantially cylindrical shape, and comprises a proximal end able to be stoppered by a plunger stopper, a distal end wherein the pharmaceutical composition is expelled from the container, and a lateral wall extending between the proximal end and the distal end of the container. In practice, the plunger stopper is aimed at moving, upon the pressure exerted by a plunger, from a proximal end of the container towards the distal end of the container, thereby expelling the drug contained into the container.

[0005] When compared to empty injection devices that are filled with a vial-stored pharmaceutical composition just prior to the injection to the patient's body, the use of prefilled injection devices leads to several advantages. In particular, by limiting the preparation prior to the injection, the prefilled injection devices provide a reduction of medical dosing errors, a minimized risk of microbial contamination and an enhanced convenience of use for the practitioners. Furthermore, such prefilled containers may encourage and simplify selfadministration by the patients which allows reducing the cost of therapy and increasing the patient adherence. Finally, prefilled injection devices reduce loss of valuable pharmaceutical composition that usually occurs when a pharmaceutical composition is transferred from a vial to a non-prefilled injection device. This results in a greater number of possible injections for a given manufacturing batch of pharmaceutical composition thus reducing buying and supply chain costs.

[0006] Prefilled injection devices can be used to carry out the injection of a plurality of compositions to a patient. In such case, the container may include two chambers, including a first chamber adapted to contain a first composition and a second chamber adapted to contain a second composition. The two chambers are separated by a second stopper that may be termed as a sequential or valved stopper that prevents the compositions from passing from one chamber to the other and mixing. The valved stopper is provided with an opening or slit of a small diameter that is sufficient to prevent the mixing of the two solutions before the first solution has been injected, while allowing subsequent injection of the second solution.

[0007] Prefilled injection devices as described above are usually obtained by filling an empty medical container with a desired pharmaceutical composition, then stoppering the filled container under vacuum or by vent tube or a combination of both.

[0008] A filled container is generally stoppered right after filing of the drug into the container body using stoppering machines according to the following method: the medical container to be stoppered is positioned on an adapted support (for example, in a nest or clipped directly on the stoppering machine), with its proximal end up, that is with its distal end down and maintained in this position.

[0009] In the case of vent tube stoppering, the stopper is compressed in a tube, usually called a “vent tube,” whose outer diameter is smaller than the inner diameter of the container. Upon placement of the stopper within the vent tube, the vent tube is then partially positioned within the container and, with the outer diameter of the vent tube being smaller than the inner diameter of the container, air is allowed to circulate between the vent tube and the container during such placement. With the vent tube positioned within the container, the stopper, previously positioned inside the tube, is then pushed distally by an installation rod out of the vent tube and to a desired position within the container above the composition (e.g., towards the proximal end of the container).

[0010] In known vent tube stoppering systems, the installation rod used to push the stopper is a simple cylindrical rod configured to pass through the center of the vent tube and into a plunger rod thread or cavity of the stopper. With the installation rod engaged with the cavity of the stopper, the installation rod is able to apply a forward pushing force to the bottom of the internal cavity, which thereby stretches the stopper while it is in the vent tube and makes it easier to pass the stopper through the tube.

[0011] While the pushing force applied by an installation rod into the cavity of a stopper works well for pushing typical sealing stoppers out from the vent tube, the unique structure of a valved stopper (as described above) may make such installation rods unsuitable for pushing valved stoppers out from the vent tube. That is, as the valved stopper includes an opening/slit valve in the bottom of its cavity, use of a traditional installation rod to engage and push the valved stopper may cause the installation rod to open the valve slit and "impale " the stopper instead of pushing it - thereby not only damaging the stopper valve, but making proper insertion impossible due to axial and total distortion of the stopper shape. Additionally, with the installation rod applying a pushing force only to the center portion of the valved stopper, it is possible for the stopper to tilt as it is being pushed out of the vent tube and into the container - with the result being that the stopper may not form a proper seal with the container wall when pushed into position.

[0012] Accordingly, a need exists in the art for a vent tube stoppering system having an installation rod suitable for use in pushing a valved stopper out from the vent tube and into a desired position within a container, while preventing damage to the stopper.

SUMMARY OF THE INVENTION

[0013] Provided herein is a vent tube stoppering system for positioning a stopper within a syringe barrel. The system includes a vent tube configured to be inserted into a chamber of the syringe barrel, with the vent tube being moveable along a longitudinal axis between a proximal tube rest position where the vent tube is outside the chamber of the syringe barrel and a distal tube operative position where a distal portion of the vent tube is positioned within the chamber of the syringe barrel, the vent tube having an internal volume configured to contain the stopper in a compressed state. The system also includes an installation rod moveable inside the internal volume of the vent tube along the longitudinal axis between a proximal rod rest position and a distal rod operative position, wherein the installation rod pushes the stopper distally out of the vent tube and into the syringe barrel when the vent tube is in the distal tube operative position. The installation rod comprises a shouldered distal end including a shoulder portion having a first diameter and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter. When pushing the stopper distally out of the vent tube, the tip portion engages a bottom surface of a cavity formed in the stopper to apply a first pressure thereto, and the shoulder portion engages a proximal face of the stopper to apply a second pressure thereto.

[0014] In certain configurations, the tip portion has a first height and the cavity formed in the stopper has a second height that is less than the first height, the cavity having the second height when compressed within the vent tube.

[0015] In certain configurations, the first height of the tip portion is approximately 3-8% greater than the second height of the cavity formed in the stopper.

[0016] In certain configurations, the tip portion applies the first pressure to the bottom surface of the cavity before the shoulder portion engages the proximal face of the stopper to apply the second pressure thereto.

[0017] In certain configurations, the first pressure is 1 to 10 Newtons.

[0018] In certain configurations, the first pressure stretches the stopper in the distal direction, so as to prevent the stopper from binding within the vent tube.

[0019] In certain configurations, the bottom surface of the cavity includes a slit formed therein, and wherein the first pressure is less than a pressure required to push the tip portion through the slit.

[0020] In certain configurations, the vent tube stoppering system further includes a container holder configured to receive a proximal end of the syringe barrel and to hold the syringe barrel aligned with the direction of travel of the vent tube, so that when moving from the proximal tube rest position to the distal tube operative position, the vent tube enters the syringe barrel. [0021] Also provided herein is a method for vent tube stoppering a syringe barrel with a valved stopper using a vent tube stoppering system. The method includes providing a vent tube stoppering system comprising a vent tube having an internal volume and configured to be inserted into a chamber of the syringe barrel, and an installation rod moveable inside the internal volume of the vent tube, the installation rod including a shouldered distal end comprising a shoulder portion having a first diameter and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter. The method also includes positioning the valved stopper within the internal volume of the vent tube, the valved stopper being contained within the stopper in a compressed state. The method further includes moving the vent tube along a longitudinal axis from a proximal tube rest position where the vent tube is outside the chamber of the syringe barrel to a distal tube operative position where a distal portion of the vent tube is positioned within the chamber of the syringe barrel and, with the vent tube in the distal tube operative position, pushing the installation rod distally through the vent tube from a proximal rod rest position to a distal rod operative position, so as to push the valved stopper distally out of the vent tube and into the syringe barrel. In pushing the valved stopper with the installation rod, the method further includes engaging a bottom surface of a cavity in the valved stopper with the tip portion, the tip portion applying a first pressure to the bottom surface causing the valved stopper to axially stretch, and engaging a proximal face of a lateral wall of the valved stopper with the shoulder portion, the tip portion applying a second pressure to the proximal face.

[0022] In certain configurations, the first pressure axially stretches the stopper in the distal direction, so as to prevent the stopper from binding within the vent tube.

[0023] In certain configurations, engaging the bottom surface of the cavity with the tip portion comprises inserting the tip portion, having a first height, into the cavity, having a second height that is less than the first height when the valved stopper is compressed within the vent tube.

[0024] In certain configurations, the first height of the tip portion is approximately 3-8% greater than the second height of the cavity.

[0025] In certain configurations, the tip portion applies the first pressure to the bottom surface of the cavity before the shoulder portion engages the proximal face of the lateral wall to apply the second pressure thereto.

[0026] In certain configurations, the first pressure is 1 to 10 Newtons.

[0027] In certain configurations, the bottom surface of the cavity includes a slit valve formed therein, and the first pressure is less than a pressure required to push the tip portion through the slit valve.

[0028] In certain configurations, the vent tube stoppering system further comprises a container holder configured to receive a proximal end of the syringe barrel, and the method further comprises coupling the container holder to the syringe barrel to hold the syringe barrel aligned with the direction of travel of the vent tube, so that when moving the vent tube along the longitudinal axis from the proximal tube rest position to the distal tube operative position, the vent tube enters the syringe barrel.

[0029] Also provided herein is a valved stopper and installation rod pair for inserting the valved stopper into a barrel of a syringe via a vent tube stoppering process. The valved stopper and installation rod pair includes a valved stopper comprising a cylindrical lateral wall extending between a proximal face and a distal face and defining a cavity therein, and a membrane positioned within the cavity and comprising a proximal surface and a distal surface, the membrane separating the cavity into a proximal cavity and a distal cavity. The valved stopper and installation rod pair also includes an elongated installation rod having a shouldered distal end configured to mate with the valved stopper, the shouldered distal end including a shoulder portion having a first diameter and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter. When the shouldered distal end is mated with the valved stopper, the tip portion is positioned in the proximal cavity and engages the proximal surface of the membrane to apply a first pressure thereto, and the shoulder portion engages the proximal face of the cylindrical lateral wall to apply a second pressure thereto.

[0030] In certain configurations, the tip portion has a first height and the proximal cavity has a second height that is less than the first height, the proximal cavity having the second height when compressed within the vent tube.

[0031] In certain configurations, the first height of the tip portion is approximately 3-8% greater than the second height of the proximal cavity formed in the valved stopper.

[0032] In certain configurations, when the shouldered distal end is mated with the valved stopper, the tip portion applies the first pressure to the proximal surface of the membrane before the shoulder portion engages the proximal face of the cylindrical lateral wall to apply the second pressure thereto.

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] FIG. 1 is a side cross-sectional view of a syringe, with which embodiments of the disclosure may be implemented;

[0034] FIG. 2A is a perspective view of a valved stopper included in the syringe of FIG. 1, according to a non-limiting embodiment described herein;

[0035] FIG. 2B is a side cross-sectional view of the valved stopper of FIG. 2A;

[0036] FIG. 3 is an exploded perspective view of a vent tube stoppering system for positioning a valved stopper within a syringe barrel, according to a non-limiting embodiment described herein;

[0037] FIG. 4 is a cross-sectional view of the vent tube stoppering system of FIG. 3, showing a vent tube and installation rod of the system in a proximal rest position;

[0038] FIG. 5 is a cross-sectional view of the vent tube stoppering system of FIG. 3, showing the vent tube and installation rod of the system in a distal operative position;

[0039] FIG. 6A is a perspective view of a distal shouldered end of the installation rod included in the system of FIG. 5 according to a non-limiting embodiment described herein;

[0040] FIG. 6B is a side cross-sectional view of the distal shouldered end of FIG. 6A; and [0041] FIG. 7 is a side cross-sectional view showing the distal shouldered end of the installation rod mated with a valved stopper.

DESCRIPTION OF THE INVENTION

[0042] The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention.

[0043] For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting. [0044] In the present disclosure, the distal end of a component or of a device means the end furthest away from the hand of the user and the proximal end means the end closest to the hand of the user, when the component or device is in the use position, i.e., when the user is holding a syringe in preparation for or during use. Similarly, in this application, the terms "in the distal direction" and "distally" mean in the direction toward the distal tip of the syringe, and the terms "in the proximal direction" and "proximally" mean in the direction opposite the direction of the distal tip of the syringe.

[0045] Referring to FIGS. 1 and 2, shown is a non-limiting embodiment of a medical container 10 with which aspects or embodiments of the disclosure may be implemented. According to aspects of the disclosure, the medical container 10 is provided as a pre-filled syringe (hereafter “ syringe 10”) that provides the convenience of rapidly delivering the liquid therein to a patient without the need to first aspirate the medication from another container and meter its volume. However, it is recognized that aspects of the disclosure may also extend to other medical containers, including cartridges and auto-injectors, as additional non-limiting examples.

[0046] As shown in FIG. 1, the syringe 10 includes a syringe barrel 12 that is formed of a generally cylindrical outer wall 16 and an end member 18 that collectively define a chamber 20 for retaining fluid therein. The syringe barrel 12 includes an open proximal end 22 and a distal end 24, with the end member 18 positioned at the distal end 24. The proximal end 22 of the syringe barrel 12 may include a flange 26 to facilitate handling and positioning of the syringe 10 and to maintain the relative position of the syringe barrel 12 with respect to a vent tube stoppering system used to insert one or more stoppers into the syringe barrel 12, as discussed in more detail below. At the distal end 24, the end member 18 may include a shoulder 28 which narrows with respect to the cylindrical outer wall 16, as well as a hub portion 30 extending out distally from shoulder 28. The hub portion 30 is formed as a partially hollow member that defines a channel 32 therethrough in fluid communication with the chamber 20. A needle 34 is attached to the hub portion 30 within channel 32, such as by being glued or otherwise secured to the hub portion 30, with the needle 34 providing for a liquid (or liquids) to be transferred out from chamber 20 and administered to a patient.

[0047] The syringe 10 also includes a pair of stoppers 36, 38 (i.e., a “sequential” stoppering) adapted to be translationally movable inside the syringe barrel 12 for injecting the liquid. The pair of stoppers 36, 38 includes a plunger stopper 36 and a sequential or “valved” stopper 38.

[0048] The plunger stopper 36 includes a closed distal surface 40 and a hollow volume 42 having a shape that corresponds to that of the distal tip of a plunger rod (not shown) that mates with the plunger stopper 36. In use of syringe 10, the plunger rod may be actuated by a user in order to advance the plunger rod and push the plunger stopper 36 in the distal direction to perform an injection.

[0049] The valved stopper 38 is positioned and arranged between the distal end 24 of the barrel and the plunger stopper 36, and is translationally movable inside the syringe barrel 12. The valved stopper 38 separates two sections of the chamber 20 in syringe barrel 12, including a first section 44 between the valved stopper 38 and the distal end 24 of the barrel 12, and a second section 46 between the valved stopper 38 and the plunger stopper 36. The first section 44 may contain a first composition, which is intended to be injected first, and the second section 46 may contain a second composition, which is intended to be injected after the first composition has been injected.

[0050] FIGS. 2A and 2B provide a more detailed view of the valved stopper 38. The valved stopper 38 may be made of any material with elastomeric properties usually used to manufacture stoppers for medical injection devices. For example, the valved stopper 38 may be made of elastomer, rubber, thermoplastic elastomer, and/or liquid silicon rubber.

[0051] The valved stopper 38 has a substantially cylindrical shape, which corresponds to the shape of the syringe barrel 12 of the syringe 10. The valved stopper 38 comprises a membrane 50, which comprises a proximal face 52 and a distal face 54. A lateral wall 56 of the valved stopper 38 extends both distally and proximally from the membrane 50. The lateral wall 56 defines a proximal cavity 58, which is a hollow volume delimited by the inner face 60 of the lateral wall and the proximal face 52 of the membrane 50, and a distal cavity 62, which is a hollow volume delimited by the inner face 60 of the lateral wall 56 and the distal face 54 of the membrane 50.

[0052] The lateral wall 56 is advantageously provided with an outer sealing surface 64 configured to sealingly engage the inner surface of the syringe barrel 12. The sealing surface 64 is continuous, which means that it extends continuously along the circumference of the valve stopper 38 and forms a ring. Since the continuous sealing surface 64 extends between the outer face of the lateral wall 56 of the valved stopper 38 and the inner surface of the syringe barrel 12 of the syringe 10, any passage of a composition between the valved stopper 38 and the syringe barrel 12 is prevented, such that optimal sealing is thus ensured. According to a preferred embodiment, the sealing surface 64 may comprise two or more sealing ribs 68. The number of ribs 68 as well as the dimensions of each rib 68, such as height, width, and the distance between two adjacent ribs 68, may be adapted to as to further optimize the sealing depending on the dimensions of the valved stopper 38 and the barrel 12.

[0053] The valved stopper 38 is further configured so that membrane 50 includes a slit or opening 70 therein. The slit 70 extends through at least a part of the thickness of the membrane 50 between the proximal face 52 and the distal face 54 thereof. The slit 70 is configured to create a fluid path through the membrane 50. The slit 70 forms a valve configured to open or close depending on the pressure exerted by a composition onto the proximal face 52 of the membrane 50. The slit 70 is preferably in the form of a line passing through the center of the proximal face 52 of the membrane 50.

[0054] According to aspects of the disclosure, a vent tube stoppering system is provided by which the valved stopper 38 may be inserted and positioned within syringe barrel 12 during assembly of the pre-filled syringe 10. The vent tube stoppering system operates to enable a desired positioning of the valved stopper 38 within syringe barrel 12, while preventing damage to the valved stopper 38 during such positioning.

[0055] Referring now to FIGS. 3-5, a vent tube stoppering system 100 (hereafter “system 100”) includes a container holder 102 configured to receive the proximal end 22 of the syringe barrel 12 to be stoppered (e.g., the flange 26 on the proximal end 22 of syringe barrel 12) and a vent device 104 operable with the container holder 102 to position a stopper (i.e., valved stopper 38) into the syringe barrel 12. [0056] The vent device 104 includes a vent tube 106 moveable through container holder 102 along a longitudinal axis (A) and an installation rod 108 moveable inside the vent tube 106 along the longitudinal axis (A), for positioning a valved stopper 38 into the syringe barrel 12 to be stoppered. The vent tube 106 is of an elongated shape, preferably of a substantially circular section, and comprises two portions 110, 112 separated by a shoulder 114 so as to form an abutment, the diameter of the second portion 112 of the vent tube being greater than the diameter of the first portion 110. In some embodiments, a flange 116 is provided on the second portion 112, at a proximal end 118 of the vent tube 106. The first portion 110 of the vent tube 106 is adapted to be inserted into the container holder 102 via a first opening 120 provided in the proximal end of the container holder 102, and has for this purpose, a smaller diameter than the first opening 120.

[0057] The vent tube 106 is configured to receive a valved stopper 38 intended to be pushed in the inner volume of said vent tube along the axis (A) by the installation rod 108. In one embodiment, the valved stopper 38 is introduced inside the vent tube 106 via an aperture 122 provided in the flange 116 (i.e., a proximal aperture 122 of vent tube 106), with the aperture 122 aligned with the axis (A).

[0058] Upon placement of the valved stopper 38 inside the vent tube 106, the first portion 110 of the vent tube 106 may be inserted into the container holder 102. The first portion 110 of the vent tube 106 is slidably engaged inside the container holder 102, and is moveable therethrough along the longitudinal axis (A), with the first portion 110 thus exiting out through a second opening 124 located at the distal end of container holder 102. In more detail, the vent tube 106 is movable between a proximal tube rest position illustrated in FIG. 4 wherein the distal end of the vent tube 106 is located within the container holder 102, in the vicinity of the first opening 120, and a distal tube operative position illustrated in FIG. 5 wherein the distal end of the vent tube 106 passes through the second opening 124 in the distal end of the container holder 102, and enters the syringe barrel 12 via the open proximal end 22 thereof, so as to be relatively close to the surface of a (first) composition contained in the syringe barrel 12.

[0059] When the vent tube 106 is pushed in the distal direction to the distal tube operative position, the first portion 110 of the vent tube 106 slides inside the container holder 102 along the axis (A) until the shoulder 114 between the first and the second portions 110, 112 of the vent tube 106 abuts the proximal end of the container holder 102. The vent tube 106 then cannot slide further towards the container holder 102. This position of the vent tube 106 relative to the container holder 102 corresponds to a maximal operative position wherein the distal end of the vent tube 106 is located inside the syringe barrel 12 at a determined position, as illustrated in FIG. 5.

[0060] In this maximal operative position, the distal end of the vent tube 106 protrudes from the distal end of the container holder 102 and into the syringe barrel 12. Yet, for positioning the valved stopper 38 inside the syringe barrel 12 after the vent tube 106 is pushed in the distal direction along the axis (A) to the maximal operative position, the installation rod 108 is then also pushed in the distal direction, thereby pushing the valved stopper 38 out of the vent tube 106 through a distal aperture 126 of the vent tube. Hence, the mechanical positioning of the valved stopper 38 is determined by the positioning of the distal aperture 126, and thus by the length by which the vent tube 106 extends into syringe barrel 12 when in the maximal operative position.

[0061] In use of the installation rod 108, the installation rod 108 is inserted in the vent tube 106, through the proximal aperture 122 formed in flange 116 of vent tube 106. As the outer diameter of the installation rod 108 is smaller than the inner diameter of the vent tube 106, the installation rod 108 may slide inside the vent tube 106 and move along the axis (A) relatively to the vent tube 106, both in a proximal and in a distal direction. To allow the positioning of the valved stopper 38 in the syringe barrel 12, the length of the installation rod 108 is longer than the length of the vent tube 106 and is adapted so that the distal end of the installation rod 108 sufficiently protrudes from the distal end of the vent tube 106 for pushing the valved stopper 38 in a desired position into the syringe barrel 12.

[0062] After the vent tube 106 with the valved stopper 38 therein is pushed in the distal direction up to the maximal operative position, the installation rod 108 is pushed also in the distal direction, from a proximal rod rest position to a distal rod operative position, wherein the installation rod 108 pushes the valved stopper 38 out of the vent tube 106 via the distal aperture 126 thereof. As a result, the valved stopper 38 is mechanically positioned in the syringe barrel 12 at a determined distance from the surface of the composition contained herein, and passes from a contracted state wherein valved stopper 38 is pressed radially against the inner surface of the vent tube 106 and has a reduced diameter, to a loosened state wherein valved stopper 38 expands radially and contacts the inner surface of the syringe barrel 12.

[0063] According to aspects of the disclosure, the distal end of the installation rod 108 is specifically configured to engage the valved stopper 38 to be inserted in syringe barrel 12, so that the installation rod 108 is able to effectively apply a pushing force to the valved stopper 38 (to advance the stopper through vent tube 106) without damage the stopper. As shown in FIGS. 6A and 6B and FIG. 7, a distal end 130 of installation rod 108 is configured as a shouldered end that includes a shoulder portion 132 and a tip portion 134, with the tip portion 134 extending out distally from the shoulder portion 132. Each of the shoulder portion 132 and the tip portion 134 are configured as generally cylindrical members. In some embodiments, a hollow channel 136 may extend through each of the portions 132, 134. The tip portion 134 is configured to have an outer diameter OD ri_p that is smaller than an outer diameter ODshouider of the shoulder portion 132 and, as can be seen in FIG. 7, the outer diameter OD i ip of the tip portion 134 is approximately equal to (but less than) an inner diameter IDcavity of the proximal cavity 58 of valved stopper 38. The outer diameter ODshouider of the shoulder portion 132 may be less than an outer diameter ODstopper of the valved stopper 38, so as to provide for easy movement of the installation rod 108 through vent tube 106.

[0064] According to embodiments, the shouldered distal end 130 of installation rod 108 is configured such that a height Hup of the tip portion 134 is slightly greater than a height/depth Hcavity of the proximal cavity 58 formed in valved stopper 38 (when the valved stopper 38 is in its compressed state within vent tube 106). In some non-limiting embodiments, the height Hup of the tip portion 134 is approximately 3-8% longer/deeper than the height/depth Hcavity of the proximal cavity 58 formed in valved stopper 38, when the valved stopper 38 is in its compressed state within the vent tube 106.

[0065] With the height of the tip portion 134 being slightly greater than the height/depth of the proximal cavity 58, the tip portion 134 is designed to apply a slight pressure to the bottom of cavity (i.e., against proximal face 52 of membrane 50) prior to the shoulder portion 132 making contact with and engaging the proximal face 138 of the valved stopper 38 (i.e., a proximal face 138 of lateral wall 56). That is, when the installation rod 108 is engaged with the valved stopper 38 and advanced to push the valved stopper 38 out distally from vent tube 106, the tip portion 134 applies a slight pressure (e.g., 1 to 10 Newtons) against proximal face 52 of membrane 50 prior to the shoulder portion 132 making contact with and engaging the proximal face of the valved stopper 38 (along lateral wall 56). The pressure applied by tip portion 134 against membrane 50 is sufficient to stretch the stopper 38 in the axial direction by an amount whereby the stopper 38 will not bind in the vent tube 106, but is low enough that the tip portion 134 will not damage or break-through the slit valve 70 during the stoppering process. Additionally, with the outer diameter ODri_p of the tip portion 134 being only slightly smaller than the outer diameter ODshouider of the shoulder portion 132, the force applied by the tip portion 134 to the membrane 50 is more around the circumference of the membrane 50 rather than in the area of slit valve 70, thereby further discouraging/preventing the tip portion 134 from damaging or breaking-through the slit valve 70. [0066] Subsequent to the initial engagement of the tip portion 134 within proximal cavity 58 and against the against membrane 50, the shoulder portion 132 then contacts a proximal face of lateral wall 56 and applies pressure thereto, such that a further pushing force applied against valved stopper 38 by installation rod 108 is more evenly distributed between the membrane 50 and the lateral wall 56. The engagement and abutment of the shoulder portion 132 against the proximal face of the lateral 56 of stopper 38 limits the travel/proj ection of tip portion 134 relative to the membrane 50, thereby preventing the tip portion 134 from piercing through the slit 70 of the membrane 50 and damaging the stopper 38.

[0067] The structure of the shouldered distal end 130 of installation rod 108 not only prevents the tip portion 134 from piercing through the slit 70 of the membrane 50 during pushing of the stopper 38, but also aids in preventing tilting of the stopper 38 as it is pushed through/out of vent tube 106. That is, the application of force (1) by the tip portion 134 to the membrane 50 around the circumference of the membrane 50 rather than in the area of slit valve 70 and (2) by the shoulder portion 132 against the proximal face 138 of lateral wall 56, helps prevent the valved stopper 38 from tilting (relative to the vent tube 106 and/or syringe barrel 12) as it is pushed by the installation rod 108 - as may be more prone to occur if an installation rod were to apply a pushing force against the stopper 38 only in the center portion of the valved stopper 38.

[0068] Beneficially, embodiments of the invention thus are directed a system and method for vent tube stoppering to place a valved stopper within a syringe barrel. The vent tube stoppering system includes an installation rod suitable for use in pushing the valved stopper out from the vent tube and into a desired position within the syringe barrel. The installation rod includes a shouldered distal end that engages the valved stopper, with a tip portion of the rod engaging a proximal cavity of the stopper and a shoulder portion engaging a proximal face of a lateral wall of the stopper. The tip portion is configured to initially engage and apply a small pressure to a bottom membrane of the cavity to axially stretch the stopper, before the shoulder portion subsequently engages the proximal face of the stopper and applies additional pressure thereto. The shouldered distal end therefore applies pressure to the stopper in a manner that enables movement thereof out of the vent tube, while preventing damage to the stopper that might occur if the distal end of the installation rod were to break-through a slit valve formed in the bottom membrane and preventing tilting of the stopper relative to the vent tube and/or syringe barrel.

[0069] Although the present disclosure has been described in detail for the purpose of illustration based on what is currently considered to be the most practical and preferred embodiments or aspects, it is to be understood that such detail is solely for that purpose and that the present disclosure is not limited to the disclosed embodiments or aspects, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

Claims

THE INVENTION CLAIMED IS

1. A vent tube stoppering system for positioning a stopper within a syringe barrel, the system comprising: a vent tube configured to be inserted into a chamber of the syringe barrel, with the vent tube being moveable along a longitudinal axis between a proximal tube rest position where the vent tube is outside the chamber of the syringe barrel and a distal tube operative position where a distal portion of the vent tube is positioned within the chamber of the syringe barrel, the vent tube having an internal volume configured to contain the stopper in a compressed state; and an installation rod moveable inside the internal volume of the vent tube along the longitudinal axis between a proximal rod rest position and a distal rod operative position, wherein the installation rod pushes the stopper distally out of the vent tube and into the syringe barrel when the vent tube is in the distal tube operative position; wherein the installation rod comprises a shouldered distal end including: a shoulder portion having a first diameter; and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter; wherein, when pushing the stopper distally out of the vent tube, the tip portion engages a bottom surface of a cavity formed in the stopper to apply a first pressure thereto, and the shoulder portion engages a proximal face of the stopper to apply a second pressure thereto.

2. The system of claim 1, wherein the tip portion has a first height and the cavity formed in the stopper has a second height that is less than the first height, the cavity having the second height when compressed within the vent tube.

3. The system of claim 2, wherein the first height of the tip portion is approximately 3-8% greater than the second height of the cavity formed in the stopper.

4. The system of claim 1, wherein the tip portion applies the first pressure to the bottom surface of the cavity before the shoulder portion engages the proximal face of the stopper to apply the second pressure thereto.

5. The system of claim 1, wherein the first pressure is 1 to 10 Newtons.

6. The system of claim 1, wherein the first pressure stretches the stopper in the distal direction, so as to prevent the stopper from binding within the vent tube.

7. The system of claim 1, wherein the bottom surface of the cavity includes a slit formed therein, and wherein the first pressure is less than a pressure required to push the tip portion through the slit.

8. The system of claim 1, further comprising a container holder configured to receive a proximal end of the syringe barrel and to hold the syringe barrel aligned with the direction of travel of the vent tube, so that when moving from the proximal tube rest position to the distal tube operative position, the vent tube enters the syringe barrel.

9. A method for vent tube stoppering a syringe barrel with a valved stopper using a vent tube stoppering system, the method comprising: providing a vent tube stoppering system comprising: a vent tube configured to be inserted into a chamber of the syringe barrel, the vent tube having an internal volume; and an installation rod moveable inside the internal volume of the vent tube, the installation rod including a shouldered distal end comprising a shoulder portion having a first diameter and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter; positioning the valved stopper within the internal volume of the vent tube, the valved stopper being contained within the stopper in a compressed state; moving the vent tube along a longitudinal axis from a proximal tube rest position where the vent tube is outside the chamber of the syringe barrel to a distal tube operative position where a distal portion of the vent tube is positioned within the chamber of the syringe barrel; and with the vent tube in the distal tube operative position, pushing the installation rod distally through the vent tube from a proximal rod rest position to a distal rod operative position, so as to push the valved stopper distally out of the vent tube and into the syringe barrel; wherein, in pushing the valved stopper with the installation rod, the method further comprises: engaging a bottom surface of a cavity in the valved stopper with the tip portion, the tip portion applying a first pressure to the bottom surface causing the valved stopper to axially stretch; and engaging a proximal face of a lateral wall of the valved stopper with the shoulder portion, the tip portion applying a second pressure to the proximal face.

10. The method of claim 9, wherein the first pressure axially stretches the stopper in the distal direction, so as to prevent the stopper from binding within the vent tube.

11. The method of claim 9, wherein engaging the bottom surface of the cavity with the tip portion comprises inserting the tip portion, having a first height, into the cavity, having a second height that is less than the first height when the valved stopper is compressed within the vent tube.

12. The method of claim 11, wherein the first height of the tip portion is approximately 3-8% greater than the second height of the cavity.

13. The method of claim 9, wherein the tip portion applies the first pressure to the bottom surface of the cavity before the shoulder portion engages the proximal face of the lateral wall to apply the second pressure thereto.

14. The method of claim 9, wherein the first pressure is 1 to 10 Newtons.

15. The method of claim 9, wherein the bottom surface of the cavity includes a slit valve formed therein, and wherein the first pressure is less than a pressure required to push the tip portion through the slit valve.

16. The method of any of claims 12-15, wherein the vent tube stoppering system further comprises a container holder configured to receive a proximal end of the syringe barrel, and wherein the method further comprises coupling the container holder to the syringe barrel to hold the syringe barrel aligned with the direction of travel of the vent tube, so that when moving the vent tube along the longitudinal axis from the proximal tube rest position to the distal tube operative position, the vent tube enters the syringe barrel.

17. A valved stopper and installation rod pair for inserting the valved stopper into a barrel of a syringe via a vent tube stoppering process, the valved stopper and installation rod pair comprising: a valved stopper comprising: a cylindrical lateral wall extending between a proximal face and a distal face, the cylindrical lateral wall defining a cavity therein; and a membrane positioned within the cavity and comprising a proximal surface and a distal surface, the membrane separating the cavity into a proximal cavity and a distal cavity; and an elongated installation rod having a shouldered distal end configured to mate with the valved stopper, the shouldered distal end including: a shoulder portion having a first diameter; and a tip portion extending out distally from the shoulder portion and having a second diameter less than the first diameter; wherein, when the shouldered distal end is mated with the valved stopper, the tip portion is positioned in the proximal cavity and engages the proximal surface of the membrane to apply a first pressure thereto, and the shoulder portion engages the proximal face of the cylindrical lateral wall to apply a second pressure thereto.

18. The pair of claim 17, wherein the tip portion has a first height and the proximal cavity has a second height that is less than the first height, the proximal cavity having the second height when compressed within the vent tube.

19. The pair of claim 18, wherein the first height of the tip portion is approximately 3-8% greater than the second height of the proximal cavity formed in the valved stopper.

20. The pair of claim 18, wherein when the shouldered distal end is mated with the valved stopper, the tip portion applies the first pressure to the proximal surface of the membrane before the shoulder portion engages the proximal face of the cylindrical lateral wall to apply the second pressure thereto.