EP4617179A1

EP4617179A1 - Stoppering tool system and method with improved stopper centering for installation in a syringe barrel

Info

Publication number: EP4617179A1
Application number: EP24305362.6A
Authority: EP
Inventors: Jérémie VAXELAIRE; Marc FLIPPE; Julien SINGER
Original assignee: Becton Dickinson France SA
Current assignee: Becton Dickinson France SA
Priority date: 2024-03-11
Filing date: 2024-03-11
Publication date: 2025-09-17
Also published as: WO2025190778A1

Abstract

Provided herein is a vent tube stoppering system for positioning a stopper within a syringe barrel. The system includes a vent tube having an insertion portion and a guide portion. The insertion portion comprises a tube-shaped member sized to be insertable into the syringe barrel and to receive the stopper in a compressed state. The guide portion comprises a tube-shaped member having an inner diameter that is greater than an inner diameter of the insertion portion. An installation rod is moveable inside the vent tube along a longitudinal axis, to enable placement of the stopper into the syringe barrel. The installation rod comprises a distal rod portion that pushes the stopper distally through the insertion portion and into the syringe barrel and a proximal rod portion comprising one or more guide features thereon that interact with the guide portion to center the installation rod relative to the vent tube.

Description

BACKGROUND OF THE INVENTION

Field of the Invention

The present disclosure relates generally to a stoppering tool system for installing a plunger stopper in a syringe and, more particularly, to a stoppering tool system for installing a plunger stopper in a syringe barrel that prevents tilting of the stopper during insertion.

Description of Related Art

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.
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.
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 self-administration 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.
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. A filled container is generally stoppered right after filling 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.
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 medical 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 medical container, air is allowed to circulate between the vent tube and the container during such placement. With the vent tube positioned within the medical container, the stopper, previously positioned inside the tube, is then pushed distally 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) by use of an installation rod.
In known vent tube stoppering systems and methods, the stopper is inserted into the vent tube at a proximal end thereof, and a separate installation rod is then used to push the stopper through the entire length of the vent tube, before the stopper exits out the distal end of the vent tube and to a desired position within the medical container. While such a method of vent tube stoppering allows for accurate placement of the stopper within the container, pushing the stopper through the entire length of the vent tube may cause the stopper to tilt. That is, with the installation rod applying a pushing force only to the center portion of the stopper, it is possible for the stopper to tilt as it is being pushed out of the vent tube and into the medical container if the installation rod is not properly centered relative to the stopper - with the result being that the stopper may not form a proper seal with the container wall when pushed into position. Tilting of the stopper may be more pronounced when the stopper is a lubricant-free or low lubricant stopper, as the amount of friction between the stopper and the vent tube is increased when the stopper is a lubricant-free or low lubricant stopper, such that the likelihood of the stopper tilting is increased. As an example, a positioning of the installation rod off center from the center portion of the stopper by 0.1 to 0.2 mm can result in stopper tilting of around 4° to 5°.
Accordingly, a need exists in the art for a vent tube stoppering system and method that reduces the potential for tilting of the stopper when being transitioned out from the vent tube into a medical container. The system and method would ensure centering of the installation rod relative to the stopper, so as to prevent tilting of the stopper as it is advanced through the vent tube, especially during vent tube stoppering of a lubricant-free or low lubricant stopper.

SUMMARY OF THE INVENTION

Provided herein is a vent tube stoppering system for positioning a stopper within a syringe barrel. The system includes a vent tube having a distal end and a proximal end, with the vent tube comprising an insertion portion and a guide portion. The insertion portion forms the distal end of the vent tube and comprises a tube-shaped member having an outer diameter that is less than an inner diameter of the syringe barrel to enable insertion thereof into the chamber of the syringe barrel and an inner diameter that enables positioning of the stopper within the insertion portion in a compressed state. The guide portion is joined to the insertion portion and forms the proximal end of the vent tube, with the guide portion comprising a tube-shaped member having an inner diameter that is greater than the inner diameter of the insertion portion. The system also includes an installation rod moveable inside the vent tube along a longitudinal axis between a proximal rod rest position and a distal rod operative position, to enable placement of the stopper into the syringe barrel. The installation rod comprises a distal rod portion configured to push the stopper distally through the insertion portion and out therefrom into the syringe barrel when in the distal rod operative position and a proximal rod portion joined to the distal rod portion, the proximal rod portion comprising one or more guide features thereon configured to interact with the guide portion to center the installation rod relative to the vent tube, as the installation rod is moved from the proximal rod rest position to the distal rod operative position.
In certain configurations, the one or more guide features comprises a first guide feature positioned at a proximal end of the proximal rod portion, the first guide feature comprising a disc-shaped flange configured to engage an inner surface of the guide portion, with the disc-shaped flange centering the installation rod relative to the vent tube.
In certain configurations, the one or more guide features comprises a second guide feature positioned at a distal end of the proximal rod portion.
In certain configurations, the second guide feature comprises a disc-shaped flange configured to engage the inner surface of the guide portion, with the disc-shaped flange centering the installation rod relative to the vent tube.
In certain configurations, the guide portion comprises an end member positioned at a distal end thereof that joins the guide portion to the insertion portion, the end member including a through-channel formed therein through which the distal rod portion may pass as the installation rod is moved from the proximal rod rest position to the distal rod operative position.
In certain configurations, the through-channel has a top opening and a bottom opening, with the bottom opening having diameter equal to the inner diameter of the insertion portion, and wherein the through-channel tapers inward from the top opening to the bottom opening thereof.
In certain configurations, the second guide feature comprises a cylindrical end member having a diameter less than the diameter of the top opening and greater than the diameter of the bottom opening, such that the cylindrical end member may engage an inner surface of the through-channel to center the installation rod relative to the vent tube.
In certain configurations, the one or more guide features comprises a single, cylindrical guide feature configured to engage the inner surface of the guide portion, with the cylindrical guide feature centering the installation rod relative to the vent tube.
In certain configurations, a length of the one or more guide features or between the one or more guide features in the longitudinal direction, L1, is equal to or greater than a collective length of the distal rod portion and the insertion portion, L2.
In certain configurations, the distal rod end of the installation rod comprises a shouldered distal end including a shoulder portion having a first rod diameter and a tip portion extending out distally from the shoulder portion and having a second rod diameter less than the first rod diameter, wherein when pushing the stopper distally out of the insertion portion of the vent tube, the tip portion engages a bottom surface of a cavity formed in the stopper and the shoulder portion engages a proximal face of the stopper.
In certain configurations, the installation rod is centered relative to the stopper within +/-0.1 mm when a ratio of rod off-centering to an outer diameter of the tip portion is equal to or less than 5%.
Also provided herein is a method for vent tube stoppering a syringe barrel using a vent tube stoppering system. The method includes inserting the stopper into the vent tube through the proximal end thereof and such that the stopper is positioned and retained within the insertion portion, at a proximal end of the insertion portion. The method also includes moving the vent tube along a longitudinal axis from a proximal tube rest position where the vent tube is outside the passageway of the syringe barrel to a distal tube operative position where a distal portion of the vent tube is positioned within the passageway of the syringe barrel. With the vent tube in the distal tube operative position, the method further includes pushing the installation rod distally through the guide portion of the vent tube and into the insertion portion, from a proximal rod rest position to a distal rod operative position, so as to push the stopper distally through and out of the insertion portion and into the syringe barrel. In pushing the installation rod distally through the guide portion of the vent tube and into the insertion portion, the one or more guide features of the installation rod interact with the guide portion to center the installation rod relative to the vent tube, so as to center the installation rod within a cavity of the stopper as the installation rod engages and pushes the stopper distally through and out of the insertion portion and into the syringe barrel.
In certain configurations, the stopper comprises a lubricant-free or low lubricant stopper.
In certain configurations, in pushing the lubricant-free or low lubricant stopper distally out of the insertion portion and into the syringe barrel, centering of the installation rod within the cavity of the stopper limits tilting of the stopper to 2° or less, and preferably 1° or less.
In certain configurations, the method further includes forming the vent tube as a single component, with the guide portion integrally formed with the insertion portion.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a syringe, with which embodiments of the disclosure may be implemented;
FIG. 2 is an exploded view of the syringe of FIG. 1;
FIG. 3 is an exploded perspective view of a vent tube stoppering system for positioning a stopper within a syringe barrel, according to a non-limiting embodiment described herein;
FIG. 4 is a cross-sectional view of a vent tube included in the vent tube stoppering system of FIG. 3, taken along line 4-4 of FIG. 3;
FIG. 5 is a side cross-sectional view of an installation rod and vent tube of the vent tube stoppering system of FIG. 3, according to a non-limiting embodiment described herein;
FIG. 6 is a side cross-sectional view of an installation rod and vent tube of the vent tube stoppering system of FIG. 3, according to another non-limiting embodiment described herein;
FIG. 7 is a side cross-sectional view of an installation rod and vent tube of the vent tube stoppering system of FIG. 3, according to another non-limiting embodiment described herein;
FIG. 8 is a side cross-sectional view of the distal end of the installation rod inserted into a cavity of a syringe stopper, according to a non-limiting embodiment described herein; and
FIG. 9 is a graphical illustration of a method for vent tube stoppering a syringe barrel with a stopper using the system of FIG. 3, according to another non-limiting embodiment described herein.

DESCRIPTION OF THE INVENTION

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.
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.
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.
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.
As shown in FIGS. 1 and 2, the syringe 10 generally includes a syringe barrel 12 and a plunger assembly 14. The plunger assembly 14 is movable within the syringe barrel 12 along a longitudinal axis to an advanced position to facilitate administering of an injectable fluid (e.g., medication) to a patient, for example. The syringe barrel 12 is formed of a generally cylindrical 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 configured to receive the plunger assembly 14 therein and a distal end 24 at which end member 18 is positioned. 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 the plunger assembly 14 during medication administration. 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. According to some aspects of the disclosure, syringe 10 may further include a cover 35 that couples to the hub portion 30 of syringe barrel 12 to protect the needle 34.
The plunger assembly 14 of syringe 10 is formed of an elongate plunger rod 36 and a plunger head or stopper 38. The plunger rod 36 may include a main body 40 extending between a plunger proximal end 42 and a plunger distal end 44. In some embodiments, the main body 40 may include a plurality of elongate vanes or walls 46 extending axially along a length thereof between the plunger proximal end 42 and the plunger distal end 44. A thumb press 48 is positioned at the plunger proximal end 42 that may be engaged by a thumb (or other finger) of the user to apply a distally directed force to the plunger assembly 14 to move the plunger rod 36 with respect to the syringe barrel 12.. In some embodiments, an extension member 50 (e.g., threaded cylindrical member) is positioned at the plunger distal end 44 that is configured to mate with the stopper 38.
The stopper 38 of plunger assembly 14 is positioned at the plunger distal end 44 so as to be movable along with the plunger rod 36 within the chamber 20 of syringe barrel 12. The stopper 38 may be made from a material that is different from the material of the plunger rod 36 and that is capable of forming a tight seal with the syringe barrel 12 as it is advanced therethrough. The stopper 38 may be formed of an elastomeric material such as butyl, styrene butadiene, isoprene, or may be formed of a polymeric material, such as cross-linked or thermoplastic elastomers, as non-limiting examples. In some embodiments, the stopper 38 may be provided as a lubricant-free or low lubricant stopper that does not include any lubricant coating or outer layer thereon, such as a coating/layer formed of per- or poly- fluoroalkyl substances (PFAS) - i.e., the stopper 38 is provided as a PFAS-free (or substantially PFAS-free) stopper. As defined herein, the stopper 38 being "free or substantially free of PFAS" or "PFAS-free" is understood to refer to materials that are entirely free of PFAS and/or materials that may contain trace amounts of PFAS therein. In an exemplary embodiment, the stopper 38 is considered to be substantially PFAS-free if it contains 200 parts-per-million (PPM) or less of PFAS therein (i.e., no more than 200 PPM), and preferably 50 PPM or less of PFAS therein (i.e., no more than 50 PPM), although it is recognized that the stopper 38 may be considered to still be "substantially PFAS-free" if it contains traces of PFAS higher than the 200 PPM indicated above, such as 300 or 400 PPM, as non-limiting examples.
The stopper 38 includes a closed distal end 52 and an open proximal end 54 providing access to a cavity 56 formed in the stopper, with the cavity 56 configured to mate with the extension member 50 on plunger rod 36. In use of syringe 10, the plunger rod 36 may be actuated by a user in order to advance the plunger rod 36 and push the stopper 38 in the distal direction to perform an injection.
According to aspects of the disclosure, a vent tube stoppering system is provided by which the 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 stopper 38 within syringe barrel 12, while preventing tilting of the stopper 38 within the syringe barrel 12 during such positioning that might result in impacting container closure integrity.
Referring now to FIGS. 3 and 4, a vent tube stoppering system 100 (hereafter "system 100") is shown in accordance with an aspect of the disclosure. The system 100 may include 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), a compression insert 104 for initially compressing the stopper 38, and a vent device 106 that receives the compressed stopper 38 from the compression insert 104 and that is operable with the container holder 102 to position the stopper 38 into the syringe barrel 12.
The compression insert 104 may be provided as a separate, static insert or component that initially receives the stopper 38 (such as from a rail system) in an uncompressed state. The uncompressed stopper 38 is advanced through a first end opening 108 of the insert 104 and into a chamber 110 thereof, with the first end opening 108 and chamber 110 having a first diameter that is equal to a diameter of the uncompressed stopper 38. In order to compress the stopper 38, the stopper 38 is then pushed/forced out through a second end opening 112 of the insert 104, which has a second diameter that is less than the diameter of the uncompressed stopper 38, such that the stopper 38 is compressed as it passes through the second end opening 112. As the stopper 38 is passed through the second end opening 112 in a compressed state, the compressed stopper 38 may be positioned within the vent device 104 (i.e., into a vent tube thereof), as explained in further detail below.
The container holder 102 may be a support structure that secures/holds the syringe barrel 12 to allow for insertion of the stopper 38 therein. According to embodiments, the container holder 102 may be provided as a nest that holds a plurality of syringe barrels therein, as known in the art, or may be provided as a holder that is clipped directly onto the stoppering machine. After the stopper 38 has been positioned within the vent device 106 (i.e., into a vent tube thereof), the vent device 106 is then positioned relative to the container holder 102, to enable positioning of the stopper 38 within the syringe barrel 12.
As shown in FIGS. 3 and 4, the vent device 106 includes a vent tube 114 moveable along a longitudinal axis (A) and an installation rod 116 moveable inside the vent tube 114 along the longitudinal axis (A), for positioning a stopper 38 into the syringe barrel 12 to be stoppered. The vent tube 114 is of an elongated shape, preferably of a substantially circular section, and comprises two tube-shaped sections or portions - i.e., an insertion portion 118 and a guide portion 120 - that are joined together and separated by an end member or shoulder 122, with an outer diameter of the guide portion 120 of the vent tube 114 being greater than the outer diameter of the insertion portion 118. The insertion portion 118 is provided at a distal end 124 of the vent tube 114 and is configured to have an outer diameter that is smaller than an inner diameter of the syringe barrel 12, such that the insertion portion 118 can be inserted into the syringe barrel 12. The guide portion 120 is provided at a proximal end 126 of the vent tube 114 and is configured to have a larger diameter than the syringe barrel 12 (and larger than the insertion portion 118), such that the guide portion 120 is prevented from being inserted into the syringe barrel 12, but instead serves as a stop.
As shown in FIG. 4, the vent tube 114 defines an internal passageway 128 therein that extends through a length of the vent tube 114 - from a proximal opening 130 of the vent tube 114 (formed in guide portion 120) to a distal opening 132 of the vent tube 114 (formed in insertion portion 118). The passageway 128 may be described as including a proximal portion 134 and a distal portion 136 - with the proximal portion 134 of passageway 128 formed through guide portion 120 and having a first diameter, D1, and the distal portion 136 of passageway 128 formed through insertion portion 118 and having a second diameter, D2, that is smaller than the first diameter D1. The second diameter, D2, of distal portion 136 of passageway 128 formed through insertion portion 118 is sized to receive the stopper 38 therein when in a compressed state.
In some embodiments, the end member or shoulder 122 is configured so as to taper the internal passageway 128 as it transitions from the proximal portion 134 to the distal portion 136. That is, the shoulder 122 may include a through-channel 138 formed therein (that forms part of passageway 128) having a top opening 140 and a bottom opening 142, with the bottom opening 142 having a diameter equal to the second diameter, D2, with the through-channel 138 tapering inward from the top opening 140 to the bottom opening 142.
The installation rod 116 may be characterized as generally including a distal rod portion 144 and a proximal rod portion 146. The distal rod portion 144 is configured to engage and push the stopper 38 distally through the insertion portion 118 of vent tube 114 and out therefrom into the syringe barrel. The proximal rod portion 146 is joined to the distal rod portion 144 and is configured to interact with the guide portion 120 of vent tube 114 to center the installation rod 116 relative to the vent tube 114.
The distal rod portion 144 is configured to have an outer diameter that is smaller than the inner diameter of the internal passageway 128 (i.e., smaller than the diameter, D2, of the distal portion 136 of the passageway 128), such as within 0.5 mm of the inner diameter distal portion 136, so that the installation rod 116 may slide inside the insertion portion 118 and move along the axis (A) relative to the vent tube 114, both in a proximal and in a distal direction. In some embodiments, to provide for positioning of the stopper 38 in the syringe barrel 12, the length of the distal rod portion 144 of installation rod 116 may be longer than the length of the vent tube 114 and may be adapted so that an end of distal rod portion 144 of the installation rod 116 sufficiently protrudes from the distal end 124 of the vent tube 114 for pushing the stopper 38 in a desired position into the syringe barrel 12.
The distal rod portion 144 of the installation rod 116 is configured to engage the stopper 38 to be inserted in syringe barrel 12, so that the installation rod 116 is able to effectively apply a pushing force to the stopper 38 (to push the stopper 38 out from vent tube 114). According to some aspects of the disclosure, the distal rod portion 144 of installation rod 116 may be configured to include a shouldered end that includes a shoulder portion 148 and a tip portion 150, with the tip portion 150 extending out distally from the shoulder portion 148. Each of the shoulder portion 148 and the tip portion 150 are configured as generally cylindrical members. The tip portion 150 is configured to be positioned within the proximal cavity 56 of stopper 38, while the shoulder portion 148 is configured to make contact with and engage a proximal face of the stopper 38. The tip portion 150 may thus be sized to have an outer diameter, OD_tip, of appropriate size to fit within and engage the proximal cavity 56 of stopper 38 (see FIG. 8).
The proximal rod portion 146 of the installation rod 116 includes one or more guide features 152 thereon configured to interact with the guide portion 120 of vent tube 114 to center the installation rod 116 relative to the vent tube 114, as the installation rod 116 is moved from a proximal rod rest position to a distal rod operative position. That is, as the installation rod 116 is moved from a proximal rod rest position where the installation rod 116 is positioned entirely outside of the vent tube 114 (or where the distal rod portion 144 is only partially positioned within the guide portion 120 of vent tube 114), to a distal rod operative position where the distal rod portion 144 is advanced into/through the insertion portion 118 of vent tube 114, the one or more guide features 152 engage the guide portion 120 of vent tube 114 to keep the installation rod 116 centered relative to the vent tube 114.
Referring now to FIGS. 5-7, the one or more guide features 152 on proximal rod portion 146 may be provided in a number of suitable configurations or constructions.
In accordance with one embodiment of the disclosure, and as shown in FIG. 5, the one or more guide features 152 comprise a first guide feature 152a positioned at a proximal end of the proximal rod portion 146 and a second guide feature 152b positioned at a distal end of the proximal rod portion 146. Each of the first guide feature 152a and the second guide feature 152b is formed as a disc-shaped flange configured to engage an inner surface of the guide portion 120 (i.e., slide along the proximal portion 134 of internal passageway 128), with the disc-shaped flanges 152a, 152b centering the installation rod 116 relative to the vent tube 114. The first and second disc-shaped flanges 152a, 152b may be spaced apart in the longitudinal direction by a distance or length, L1.
In accordance with another embodiment of the disclosure, and as shown in FIG. 6, the one or more guide features 152 comprise a first guide feature 152a positioned at a proximal end of the proximal rod portion 146 and a second guide feature 152b positioned at a distal end of the proximal rod portion 146. The first guide feature 152a is formed as a disc-shaped flange configured to engage an inner surface of the guide portion 120 (i.e., slide along the proximal portion 134 of internal passageway 128). The second guide feature 152b is formed as a cylindrical end member (i.e., positioned at a distal end of the proximal rod portion 146) having a diameter smaller than the first diameter, D1, of the proximal portion 134 of passageway 128 formed through guide portion 120 but greater than the second diameter, D2, of the distal portion 136 of passageway 128 formed through insertion portion 118. The cylindrical end member 152b may be configured to be partially received within the through-channel 138 of shoulder, with the diameter thereof being less than the diameter of the top opening 140 of through-channel 138 and greater than the diameter of the bottom opening 142 of through-channel 138. Thus, as the installation rod 116 is moved from its proximal rod rest position to its distal rod operative position, the cylindrical end member 152b may engage an inner surface of the through-channel 138 to center the installation rod 116 relative to the vent tube 114. The disc-shaped flange 152a and the cylindrical end member 152b may be spaced apart in the longitudinal direction by a distance or length, L1.
In accordance with another embodiment of the disclosure, and as shown in FIG. 7, the one or more guide features 152 comprise a single, cylindrical guide feature 152c extending along a length of the proximal rod portion 146. The cylindrical guide feature 152c is configured to engage the inner surface of the guide portion 120 (i.e., slide along the proximal portion 134 of internal passageway 128), with the cylindrical guide feature 152c centering the installation rod 116 relative to the vent tube 114. The cylindrical guide feature 152c may have length, L1, in the longitudinal direction.
According to embodiments of the disclosure, for each of the installation rods 116 shown in FIGS. 5-7, the installation rod 116 may be designed so that the distance/length between first and second guide features 152a, 152b (or the length of the single cylindrical guide feature 152c) in the longitudinal direction, L1, is equal to or greater than a collective length, L2, of the distal rod portion 144 and the insertion portion 118 of vent tube 114. By designing the installation rod 116 (and vent tube 114) in such a manner, the stabilization and guiding provided by the guide feature(s) 152 is maximized/optimized, to ensure centering of the installation rod 116 centered relative to the vent tube 114.
By centering the installation rod 116 relative to the vent tube 114 via inclusion of guide feature(s) 152 on the installation rod 116 (and interaction thereof with guide portion 120 of vent tube 114), the shouldered end (i.e., shoulder portion 148 and the tip portion 150) of distal rod portion 144 may be centered relative to stopper 38 when it is engaged therewith and may remain centered relative to stopper 38 as the installation rod 116 is advanced from its proximal rod rest position to its distal rod operative position. That is, as shown in FIG. 8, the tip portion 150 may be centered within the proximal cavity 56 of stopper 38. With the tip portion 150 of installation rod 116 centered within the proximal cavity 56 of stopper 38, a proper orientation of the stopper 38 may be maintained as it is pushed distally through the insertion portion 118 of vent tube 114 - i.e., tilting of the stopper 38 off of the longitudinal axis is minimized/prevented. According to embodiments of the disclosure, tilting of the stopper 38 may be limited to 2° or less, and preferably 1° or less. As a non-limiting example, tilting of the stopper 38 may be limited to an acceptable amount when the installation rod 116 is centered relative to the stopper 38 within +/- 0.1 mm of center. In some embodiments, centering of the installation rod 116 within +/- 0.1 mm of center of the stopper 38 may be ensured when a ratio of rod off-centering to an outer diameter of the tip portion, OD_tip, is equal to or less than 5%.
Referring now to FIG. 9, and with continued reference to FIGS. 1-7, a method 154 for vent tube stoppering the syringe barrel 12 with stopper 38 using the vent tube stoppering system 100 of FIGS. 3-7 is described, according to aspects of the disclosure. The method 154 begins at Step 156 with the receiving of stopper 38 in an uncompressed state and the providing thereof to vent tube 114. In some embodiments, the stopper 38 may exit a rail device or system (not shown). At shown at Step 156, a compression insert 104 may be positioned adjacent the proximal end of the insertion portion 118 of vent tube 114 and may be secured thereto, with the stopper 38 then moved so as to be positioned adjacent the compression insert 104, so as to provide for transitioning of the stopper 38 from the compression insert 104 directly into the insertion portion 118 of vent tube 114. With the compression insert 104 positioned adjacent the proximal end of insertion portion 118 of vent tube 114 and the stopper 38 deposited adjacent the compression insert 104, the stopper 38 may then be forced into a chamber 110 of the compression insert 104 at Step 158, such as by a push rod 157. That is, the uncompressed stopper 38 is advanced though a first end opening 108 of the compression insert 104 and into chamber 110 thereof responsive to a pushing force applied by insertion rod 148. As the first end opening 108 of insert 104 has a first diameter that is equal to a diameter of the uncompressed stopper 38, the stopper 38 is initially provided into compression insert 104 in an uncompressed state. Also at Step 158, with the insertion rod 148 continuing to apply a pushing force to the stopper 38, the stopper 38 is pushed/forced out through the second end opening 112 of the insert 104, which has a second diameter that is less than the diameter of the uncompressed stopper 38, such that the stopper 38 is compressed as it passes through the second end opening 112. As the stopper 38 is passed through the second end opening 112 in its compressed state, the compressed stopper 38 is positioned within the proximal end of insertion portion 118 of vent tube 114.
With the compressed stopper 38 retained within the insertion portion 118 of vent tube 114, the push rod 157 and compression insert 104 may be removed from vent tube 114 at Step 160 and the vent tube 114 may be moved to a location proximate the syringe barrel 12 at Step 162 - with it recognized that syringe barrel 12 is secured/retained in container holder 102, which may be a nest for example. Upon the vent tube 114 being aligned with the syringe barrel 12, the vent tube 114 may be moved from its proximal tube rest position (where the distal end 124 of the vent tube 114 is located outside the syringe barrel 12) to its distal tube operative position (where the distal end 124 of the vent tube 114 enters into the syringe barrel 12 via the open proximal end 22 thereof) at Step 164, so as to be relatively close to the surface of a fluid/medicament contained in the syringe barrel 12. When the vent tube 114 is pushed in the distal direction to the distal tube operative position, the insertion portion 118 of the vent tube 114 slides inside the syringe barrel 12 along the axis (A) until the shoulder 122 between the insertion portion 118 and guide portion 120 of the vent tube 114 abuts the proximal end 22 of the syringe barrel 12. The vent tube 114 then cannot slide further towards the syringe barrel 12. This position of the vent tube 114 relative to the syringe barrel 12 corresponds to a maximal operative position wherein the distal end 124 of the vent tube 114 is located inside the syringe barrel 12 at a determined position.
With the vent tube 114 moved to its maximal operative position relative to the syringe barrel 12, the installation rod 116 is then aligned with vent tube 114 and pushed through the passageway 128 of vent tube 114 in the distal direction at Steps 166-170 - from its proximal rod rest position (Step 160), further distally to an intermediate position (Step 168), and finally to its distal rod operative position (Step 170). When advanced into and through the passageway 128 toward the distal rod operative position, the installation rod 116 is centered relative to the vent tube 114 via interaction of the guide feature(s) 152 on installation rod 116 with the guide portion 120 of vent tube 114. That is, one or more guide features 152 on the proximal rod portion 146 engage the inner surface of the guide portion 120 (i.e., slide along the proximal portion 134 of internal passageway 128), with the guide feature(s) 152 centering the installation rod 116 relative to the vent tube 114. In some embodiments, a guide feature 152 on the proximal rod portion 146 may also engage the through-channel 138 of shoulder 122 to center the installation rod 116 relative to the vent tube 114
As the installation rod 116 is pushed through the passageway 128 of vent tube 114, the shouldered end (i.e., shoulder portion 148 and tip portion 150) of the distal rod portion 144 of installation rod 116 is brought into contact with stopper 38, which is positioned/retained in the proximal end of insertion portion 118 of vent tube 114. As the installation rod 116 is advanced toward the distal rod operative position, the installation rod 116 pushes the stopper 38 distally through the insertion portion 118 and out of the distal end 124 of vent tube 114 via the distal opening 132 thereof. As a result, the stopper 38 is mechanically positioned in the syringe barrel 12 at a determined distance from the surface of the fluid/medicament contained herein, and passes from a contracted state wherein stopper 38 is pressed radially against the inner surface of the insertion portion 118 of vent tube 114, to a loosened state wherein stopper 38 expands radially and contacts the inner surface of the syringe barrel 12. Subsequent to positioning of the stopper 38 within syringe barrel 12, the vent tube 114 may then be withdrawn proximally from syringe barrel 12 at Step 172.
According to aspects of the disclosure, by guiding advancement of the installation rod 116 through vent tube 114 and ensuring centering of the installation rod 116 relative to the vent tube 114, the distal rod portion 144 of installation rod 116 engages the stopper 38 in a centered alignment - i.e., tip portion 150 is centered within cavity 56 of stopper 38. With the tip portion 150 centered within cavity 56 of stopper 38, the stopper 38 may be pushed through the insertion portion 118 of vent tube 114 by installation rod 116 in a manner that prevents/minimizes tilting of the stopper 38 relative to the longitudinal axis A, as might occur if the tip portion 150 were positioned off-center within cavity 56 of stopper 38. With tilting of the stopper 38 minimized/prevented in this manner, the stopper 38 may form a tight seal with the syringe barrel 12 as it is pushed out of the vent tube 114 and into the syringe barrel 12. The minimizing/preventing of tilting of the stopper 38 as it is pushed distally through insertion portion 118 of vent tube 114 may be especially beneficial for lubricant-free or low lubricant stoppers (e.g., PFAS-free stoppers) that present higher friction during vent tube stoppering.
Beneficially, embodiments of the invention thus are directed a system and method for vent tube stoppering to place a stopper within a syringe barrel. The vent tube stoppering system includes a vent tube having a guide portion at the proximal end thereof. Guide feature(s) are provided on the installation rod that interact with the guide portion to ensure the installation rod remains centered relative to the vent tube as it is advanced distally therethrough, such that the installation rod also is centered relative to the stopper when it comes into engagement therewith. By centering the stopper on the distal end of the installation rod, the stopper may be pushed through an insertion portion of the vent tube in a manner that prevents/minimizes tilting of the stopper when it is pushed out from the vent tube and into the syringe barrel. With tilting of the stopper minimized/prevented in this manner, the stopper may form a tight seal with the syringe barrel and ensure container closure integrity.
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

A vent tube stoppering system for positioning a stopper within a chamber of a syringe barrel, the system comprising:
a vent tube having a distal end and a proximal end, the vent tube comprising:
an insertion portion forming the distal end of the vent tube, the insertion portion comprising a tube-shaped member having an outer diameter that is less than an inner diameter of the syringe barrel to enable insertion thereof into the chamber of the syringe barrel and an inner diameter that enables positioning of the stopper within the insertion portion in a compressed state; and

a guide portion joined to the insertion portion and forming the proximal end of the vent tube, the guide portion comprising a tube-shaped member having an inner diameter that is greater than the inner diameter of the insertion portion; and

an installation rod moveable inside the vent tube along a longitudinal axis between a proximal rod rest position and a distal rod operative position, to enable placement of the stopper into the syringe barrel, wherein the installation rod comprises:
a distal rod portion configured to push the stopper distally through the insertion portion and out therefrom into the syringe barrel when in the distal rod operative position; and

a proximal rod portion joined to the distal rod portion, the proximal rod portion comprising one or more guide features thereon configured to interact with the guide portion to center the installation rod relative to the vent tube, as the installation rod is moved from the proximal rod rest position to the distal rod operative position.
The system of claim 1, wherein the one or more guide features comprises a first guide feature positioned at a proximal end of the proximal rod portion, the first guide feature comprising a disc-shaped flange configured to engage an inner surface of the guide portion, with the disc-shaped flange centering the installation rod relative to the vent tube.
The system of claim 2, wherein the one or more guide features comprises a second guide feature positioned at a distal end of the proximal rod portion.
The system of claim 3, wherein the second guide feature comprises a disc-shaped flange configured to engage the inner surface of the guide portion, with the disc-shaped flange centering the installation rod relative to the vent tube.
The system of any of claims 1-4, wherein the guide portion comprises an end member positioned at a distal end thereof that joins the guide portion to the insertion portion, the end member including a through-channel formed therein through which the distal rod portion may pass as the installation rod is moved from the proximal rod rest position to the distal rod operative position.
The system of any of claims 1-5, wherein the through-channel has a top opening and a bottom opening, with the bottom opening having diameter equal to the inner diameter of the insertion portion, and wherein the through-channel tapers inward from the top opening to the bottom opening thereof.
The system of any of claims 1-6, wherein the second guide feature comprises a cylindrical end member having a diameter less than the diameter of the top opening and greater than the diameter of the bottom opening, such that the cylindrical end member may engage an inner surface of the through-channel to center the installation rod relative to the vent tube.
The system of any of claims 1-7, wherein the one or more guide features comprises a single, cylindrical guide feature configured to engage the inner surface of the guide portion, with the cylindrical guide feature centering the installation rod relative to the vent tube.
The system of any of claims 1-7, wherein a length of the one or more guide features or between the one or more guide features in the longitudinal direction, L1, is equal to or greater than a collective length of the distal rod portion and the insertion portion, L2.
The system of any of claims 1-8, wherein the distal rod end of the installation rod comprises a shouldered distal end including:
a shoulder portion having a first rod diameter; and

a tip portion extending out distally from the shoulder portion and having a second rod diameter less than the first rod diameter;

wherein, when pushing the stopper distally out of the insertion portion of the vent tube, the tip portion engages a bottom surface of a cavity formed in the stopper and the shoulder portion engages a proximal face of the stopper.
The system of claim 10, wherein the installation rod is centered relative to the stopper within +/- 0.1 mm when a ratio of rod off-centering to an outer diameter of the tip portion is equal to or less than 5%.
A method for vent tube stoppering a syringe barrel with a stopper using the vent tube stoppering system of claim 1, the method comprising:
inserting the stopper into the vent tube through the proximal end thereof and such that the stopper is positioned and retained within the insertion portion, at a proximal end of the insertion portion;

moving the vent tube along a longitudinal axis from a proximal tube rest position where the vent tube is outside the passageway of the syringe barrel to a distal tube operative position where a distal portion of the vent tube is positioned within the passageway of the syringe barrel; and

with the vent tube in the distal tube operative position, pushing the installation rod distally through the guide portion of the vent tube and into the insertion portion, from a proximal rod rest position to a distal rod operative position, so as to push the stopper distally through and out of the insertion portion and into the syringe barrel;

wherein in pushing the installation rod distally through the guide portion of the vent tube and into the insertion portion, the one or more guide features of the installation rod interact with the guide portion to center the installation rod relative to the vent tube, so as to center the installation rod within a cavity of the stopper as the installation rod engages and pushes the stopper distally through and out of the insertion portion and into the syringe barrel.
The method of claim 12, wherein the stopper comprises a lubricant-free or low lubricant stopper.
The method of claim 13, wherein in pushing the lubricant-free or low lubricant stopper distally out of the insertion portion and into the syringe barrel, centering of the installation rod within the cavity of the stopper limits tilting of the stopper to 2° or less, and preferably 1° or less.
The method of any of claims 11-14, further comprising forming the vent tube as a single component, with the guide portion integrally formed with the insertion portion.