Injection device for drug delivery and packaging for injection device

Abstract

To provide an injection device including: a syringe having a barrel and a flange; and a backstop configured to be coupled with the syringe adjacently to the flange.SOLUTION: The backstop includes an inner surface generally extending around at least a portion of the syringe. The inner surface includes at least one protrusion 150. The at least one protrusion 150 extends away from the inner surface and is configured to engage the flange and / or the barrel to permit or promote an airflow through a space between the inner surface and the syringe.SELECTED DRAWING: Figure 2B

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 895,456, filed September 3, 2019, and U.S. Provisional Patent Application No. 63 / 018,141, filed April 30, 2020, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to injection devices and packaging for injection devices for drug delivery. More specifically, the present disclosure relates generally to a detent for an injection device that improves grip, usability and / or ergonomic design of the injection device and / or reduces or prevents inadvertent movement of a plunger rod and / or a stopper component associated with the injection device or packaging for identifying, securing and / or holding the injection device. [Background technology]

[0003] As is well known in the art, a syringe is a medical delivery device used to administer medication to a patient. Syringes are often commercially available either in a pre-filled form, in which a set dose of medication is already provided therein, or in an empty state, which is intended to be filled by the end user from a vial or other source of medication when administration of the medication is desired.

[0004] Syringes often include a barrel portion adapted to hold a medicament. The distal end of the barrel is often configured to include and / or mate with a conventional piercing element, such as a pointed needle cannula or a cannula with a blunt end, to deliver the medicament contained within the barrel. The piercing element may be made of steel, plastic, or any other suitable material. A plunger rod may be inserted through the open proximal end of the syringe barrel, and engagement of the plunger rod with an elastomeric or rubbery stopper element mounted in a substantially fluid-tight manner within the interior of the barrel allows a user to apply manual force to the plunger to deliver the medicament through the piercing element. A flange is also often provided around the open distal end of the syringe barrel as a form of finger rest to facilitate manipulation of the device by the user. The syringe may also include a detent or a component (also known as a "detent") coupled or connected to the flange to improve grip, usability, and / or ergonomic design of the syringe. As a more specific example, the detent may have a radial length greater than the length of the flange, thereby effectively extending the length of the gripping surface. The detent and / or plunger rod may also or alternatively reduce or prevent inadvertent movement of the plunger rod and / or stopper components. As a more specific example, the detent and / or plunger rod may have components that engage with each other to define a maximum point in the retracted direction that the plunger rod may travel.

[0005] For both drug integrity and patient safety, it may be desirable to thoroughly sterilize the components of the syringe. Sterilization may occur at several stages of the assembly process, including pre-filling (e.g., sterilization of the empty barrel and / or plunger) and post-filling (e.g., external sterilization of the assembled pre-filled syringe). External sterilization typically occurs after the pre-filled syringe is filled, fully assembled, and placed in at least some parts of its final package. Federal regulations may require external sterilization under certain conditions, parameters, and / or results for some applications of use, such as certain ophthalmic applications. Summary of the Invention [Problem to be solved by the invention]

[0006] External sterilization can be a design challenge. For example, drugs may be sensitive to sterilization and / or conditions, such as temperature, gas, radiation, etc. Furthermore, it may be difficult to achieve a desired or necessary level of sterilization of the syringe and / or its components, especially in view of drug sensitivity. As a more specific example, surface interactions between various components of the syringe and / or packaging may create or promote occlusion spaces that may not be effectively and / or completely sterilized during the external sterilization step performed on the syringe. As a more specific example, surface interactions between the syringe and the detent and / or between the syringe and the packaging may create or promote occlusion spaces. If occlusion spaces prevent or impede effective levels of sterilizing gas from reaching an area, the area may not be effectively sterilized. If occlusion spaces prevent or impede sterilizing gas from being purged from an area, a patient, such as a patient who is already visually immunocompromised prior to treatment, may develop a more severe condition, such as a superficial eye infection or endophthalmitis. It is therefore desirable to achieve an adequate level of sterility of all relevant parts and components of the syringe while maintaining the integrity of the drug. [Means for solving the problem]

[0007] The present disclosure describes an injection device that embodies an advantageous alternative to existing injection devices and their packaging, and that can address one or more of the problems or needs set forth herein, as well as provide other benefits and advantages.

[0008] An injection device is provided that includes a syringe having a barrel and a flange, and a detent configured to be coupled to the syringe adjacent the flange. The detent may have an inner surface generally extending around at least a portion of the syringe, the inner surface including at least one protrusion extending away from the inner surface and configured to engage the flange and / or the barrel to allow or facilitate air flow through a space between the inner surface and the syringe.

[0009] The injection device may include at least two protrusions extending away from the inner surface and configured to engage the flange and / or barrel to allow or promote air flow through a space between the inner surface and the syringe. The injection device may also include another number of protrusions, such as three, four, five, six, seven, or another suitable number.

[0010] The injection device may include a collar defining an inner surface generally extending around at least a portion of the barrel. The injection device may also or alternatively be configured to engage the syringe in a snap-fit ​​relationship.

[0011] The at least one protrusion may be a rib that extends generally parallel to the axis of the syringe.

[0012] The detent may define a cavity for receiving at least a portion of the flange. The cavity may include facing surfaces defining the cavity, and the at least one protrusion may extend away from at least one of the facing surfaces. The at least one protrusion may include at least one protrusion on the upper facing surface and at least one protrusion on the lower facing surface. Additionally or alternatively, the at least one protrusion may include at least two ribs on the upper facing surface and at least two ribs on the lower facing surface.

[0013] The injection device can be a pre-filled syringe containing a drug such as a VEGF inhibitor.For example, the VEGF inhibitor can be a non-antibody VEGF inhibitor.As another example, the non-antibody VEGF inhibitor can be a VEGF trap.The VEGF trap can be aflibercept.

[0014] The injection device may also or alternatively include a package configured to receive and / or support a syringe, the package including a hollow surface and at least one protrusion extending away from the hollow surface, the at least one protrusion configured to engage the barrel of the syringe to enable or promote air flow through a space between the hollow surface and the syringe.

[0015] The injection device may also or alternatively include a package configured to receive and / or support a syringe, the package including a hollow surface that engages the barrel of the syringe and defines at least one stop surface configured to prevent and / or limit movement of the plunger rod.

[0016] The present disclosure will be more fully understood upon reading the following description in conjunction with the accompanying drawings. Some of the drawings may be simplified by omitting selected elements in order to more clearly show other elements. The omission of such elements in some drawings does not necessarily indicate the presence or absence of a particular element in any of the illustrative embodiments, unless expressly described in the corresponding specification. Additionally, none of the drawings are necessarily drawn to scale. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is a perspective view of an exemplary injection device having a syringe with a barrel (partially shown), a flange, a plunger rod (partially shown), and a detent, according to an aspect of the present disclosure. [Figure 2A] FIG. 13 is a perspective view of another exemplary injection device having a barrel, a flange, and a detent in accordance with aspects of the present disclosure. [Figure 2B] FIG. 2B is an exploded perspective view of the device shown in FIG. 2A showing the detent separated from the barrel and flange. [Figure 2C] FIG. 2B is a front view of the device shown in FIG. 2A showing the barrel (partial view) and detent. [Figure 2D] FIG. 2B is a bottom view of the detent and syringe shown in FIG. 2A. [Figure 2E] FIG. 2C is a perspective view of the detent shown in FIG. 2B. [Figure 2F] FIG. 2C is a front view of the detent shown in FIG. 2B. [Figure 2G] FIG. 2C is a top view of the detent shown in FIG. 2B. [Figure 2H] FIG. 2C is a bottom view of the detent shown in FIG. 2B. [Figure 3A] FIG. 13 is a top perspective view of another example detent having a barrel, a flange, and a detent in accordance with aspects of the present disclosure. [Figure 3B] FIG. 3B is a bottom perspective view of the detent shown in FIG. 3A. [Figure 4A]FIG. 13 is a top perspective view of another example detent having a barrel, a flange, and a detent in accordance with aspects of the present disclosure. [Figure 4B] FIG. 4B is a bottom perspective view of the detent shown in FIG. 4A. [Figure 5A] FIG. 1 is a perspective view of another exemplary injection device having a barrel (partially shown), a flange, and a detent, according to an aspect of the present disclosure. [Figure 5B] FIG. 5B is a perspective view of the detent shown in FIG. 5A. [Figure 5C] FIG. 5B is a front view of the detent shown in FIG. 5A. [Figure 5D] FIG. 5B is a top view of the detent shown in FIG. 5A. [Figure 5E] FIG. 5B is a bottom view of the detent shown in FIG. 5A. [Figure 6A] FIG. 1 is a perspective view of another exemplary injection device having a barrel (partially shown), a flange, and a detent, according to an aspect of the present disclosure. [Figure 6B] FIG. 6B is a perspective view of the detent shown in FIG. 6A. [Figure 6C] FIG. 6B is a front view of the detent shown in FIG. 6A. [Figure 6D] FIG. 6B is a top view of the detent shown in FIG. 6A. [Figure 6E] FIG. 6B is a bottom view of the detent shown in FIG. 6A. [Figure 7A] FIG. 1 is a perspective view of another exemplary injection device having a barrel (partially shown), a flange, and a detent, according to an aspect of the present disclosure. [Figure 7B] FIG. 7B is a perspective view of the detent shown in FIG. 7A. [Figure 7C] FIG. 7B is a front view of the detent shown in FIG. 7A. [Figure 7D] FIG. 7B is a top view of the detent shown in FIG. 7A. [Figure 7E] FIG. 7B is a bottom view of the detent shown in FIG. 7A. [Figure 8A] FIG. 1 is a perspective view of another exemplary injection device having a barrel (partially shown), a flange, and a detent, according to an aspect of the present disclosure. [Figure 8B] FIG. 8B is a front view of the detent shown in FIG. 8A. [Figure 8C] FIG. 8B is a top view of the detent shown in FIG. 8A. [Figure 9A] FIG. 1 is a perspective view of another exemplary injection device according to aspects of the present disclosure. [Figure 9B] FIG. 9B is a front view of the detent shown in FIG. 9A. [Figure 9C] FIG. 9B is a top view of the detent shown in FIG. 9A. [Figure 9D] FIG. 9B is a bottom view of the detent shown in FIG. 9A. [Figure 10A] FIG. 1 is a perspective top view of an exemplary package that may be used to secure and / or hold an injection device, for example, during external sterilization of the injection device, according to an aspect of the disclosure. [Figure 10B] FIG. 10B is a perspective bottom view of the package shown in FIG. 10A. [Figure 10C] FIG. 11 is a perspective top view of the package shown in FIG. 10 with an exemplary injection device. [Figure 11] FIG. 13 is a perspective top view of another exemplary package that may be used to secure and / or hold an injection device, for example, during external sterilization of the injection device, according to an aspect of the disclosure. [Figure 12A] FIG. 13 is a top view of another exemplary package with a top protective cover removed, which may be used to secure and / or hold an injection device, for example, during external sterilization of the injection device, according to an aspect of the disclosure. [Figure 12B] FIG. 12B is a top view of the exemplary package shown in FIG. 12A with the top protective cover in place. [Figure 13A] 2A-2C show various perspective views of the syringe of FIG. 1 highlighting areas of the syringe that may be particularly susceptible to gas blockage during and after the external sterilization process. [Figure 13B] 2A-2C show various perspective views of the syringe of FIG. 1 highlighting areas of the syringe that may be particularly susceptible to gas blockage during and after the external sterilization process. [Figure 13C]2A-2C show various perspective views of the syringe of FIG. 1 highlighting areas of the syringe that may be particularly susceptible to gas blockage during and after the external sterilization process. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The present disclosure generally relates to an injection device that can be safely and reliably actuated by a user to administer a drug or to self-administer a drug when the patient is the user. More specifically, the present disclosure generally relates to an injection device that includes a syringe and a detent and / or package configured to receive and / or support the syringe. The injection device can be a syringe, such as a pre-filled syringe, that contains a drug. These components, whether separately or together, can be suitable for an external sterilization process. As a more specific example, the use of these components, separately or together, can allow a manufacturer or user to utilize a desired bioburden kill level while minimizing or avoiding undesirable effects on the drug.

[0019] As used herein, the term "about" means + / - 10% of the smallest significant figure.

[0020] Due to the engagement between the detents and the syringe as is known in the art, the sterilizing gas may not be able to reach the closed or partially closed spaces between each detent and the syringe, thereby failing to fully or properly sterilize these surfaces. Additionally or alternatively, the sterilizing gas may not be effectively purged from these closed or partially closed spaces, thereby exposing the drug to the sterilizing gas beyond the designated sterilization step in the chamber. Either and / or both of these situations may be undesirable. As a more specific example, Figures 13A-13C include various views of a syringe barrel and flange, the surfaces of which that may be particularly susceptible to occlusion are shown with dark shading and designated by reference numeral 11c (proximal section of barrel 11) and reference numeral 12c (proximal section of flange 12). For example, the flange top surface 12c and the barrel exterior surface 11c may be particularly susceptible to occlusion due to their respective engagement with detents as is known in the art.

[0021] FIG. 1 is a perspective view of an injection device 10, such as a syringe 10, generally having a barrel 11 having a proximal open end 11a, a distal end 11b (FIGS. 2A, 2B, 12A and 12B), a cavity 13, a flange portion 12, a plunger rod 16, a stopper component 18 (FIGS. 12A and 12B) and a return detent 20.

[0022] The syringe barrel distal end 11b includes and / or supports a needle or other suitable components for completing a fluid path to a patient. For example, the syringe barrel distal end may include a luer lock component 17 (FIGS. 2A and 2B) and / or a protective cap 19 (FIG. 12A) that covers the luer lock component 17. Prior to use, the protective cap 19 may be removed to allow the luer lock component 17 to receive a needle. The syringe barrel proximal end 11a (see FIG. 2A) may receive a plunger rod 16 for pushing the stopper component 18 in a distal direction 15 to expel the drug from the syringe 10. For example, the stopper component 18 may form a fluid-tight relationship with the cavity 13 while also moving in a distal direction 15 along the cavity 13 to push the drug out of the distal end of the syringe 10. The plunger rod 16 may include a plunger rod end 14 having a larger diameter than a body portion of the plunger rod 16 to limit the distance the plunger rod 16 travels in the distal direction 15 and / or to make it easier for a user to push the plunger rod 16. The plunger rod 16 may be a one-way component, in that the plunger rod is not fixedly connected to a stopper, so that when the plunger rod 16 travels in the proximal direction (opposite the distal direction 15), the stopper 18 does not move with the plunger rod 16.

[0023] 12A and 12B show a syringe 10 (collectively packaged syringes 8) disposed within a package 9, such as a blister pack 9. The package 9 includes a base portion 9a and a cover 9b (FIG. 12B), such as a Tyvek cover 9b, that extends substantially or completely across and / or is sealed to the base portion 9a. The Tyvek cover 9b may extend outside the perimeter of the base portion 9a in at least one portion, such as one side, to make removal of the Tyvek cover 9b easier. Additionally or alternatively, the base portion 9a may include a tab portion 9c that is not sealed by the Tyvek cover 9b to facilitate easy removal.

[0024] The syringe barrel 11 may be made of plastic, glass, or any suitable material. As a more specific example, the syringe barrel may be made of a plastic material including at least one or more of the following materials: specific grades of polypropylene (homopolymer and / or copolymer polypropylene), cycloolefin copolymer (COC), cycloolefin polymer (COP), or other suitable materials. As a more specific example, the syringe barrel may be made of cycloolefin polymer (COP).

[0025] The detent 20 may be coupled or connected to the syringe 10 to improve the grip, usability and / or ergonomic design of the syringe. The flange 12 may include a diameter larger than the diameter of the syringe barrel 11 and may serve as a finger rest to allow the user to manipulate the syringe 10 during use. For example, the user may rest two or more of their fingers on the flange 12 while using their thumb to press the plunger rod end 14. As a more specific example, the detent 20 may be coupled to the flange portion 12 to effectively extend the flange portion and thereby increase the length of the grip surface. As an even more specific example, in certain applications of the syringe, particularly in ophthalmic applications, it may be desirable for the user to have a larger effective grip surface to improve the grip, usability and / or ergonomic design of the syringe. However, due to space constraints during manufacturing and shipping, and economies of scale using standard syringe / flange configurations, it may not be desirable to increase the size of the flange portion 12. Additionally, syringes are commonly used in autoinjectors that have geometries that cannot accommodate syringes with enlarged flange sizes, and therefore, it may be desirable to have additional components, such as detent components, that can be attached and / or coupled to the syringe at the time of the manufacturing process.

[0026] The detent may be manufactured from any suitable material. For example, the detent may be molded from polypropylene ("PP") or acrylonitrile butadiene styrene ("ABS"). ABS may have the advantage of being harder than PP and other materials, making the detent lighter. As a more specific example, if the detent is made from PP, it may have a minimum wall thickness of 1.5 mm, while if the detent is made from ABS, it may have a minimum wall thickness of 1 mm.

[0027] The detent 20 may also be used to limit, restrict, reduce or prevent inadvertent movement of the stopper component 18 relative to the syringe 10. For example, the detent 20 may be fitted onto the flange 12 to reduce or prevent inadvertent movement of the plunger rod 16. For example, as shown in FIG. 1, the detent 20 may have a locking surface 34 that engages the plunger rod 16 to limit or prevent relative movement in the distal direction 15 between these two components. As a more specific example, the plunger rod 16 may have a locking ring 16a that has a larger diameter than the remainder of the plunger rod 16 but a smaller diameter than the cavity, and the locking surface 34 of the detent 20 may have a smaller diameter than the locking ring 16a such that the locking ring 16a cannot move proximally past the detent 20. This configuration would function to limit the proximal movement of the plunger rod 16.

[0028] For the reasons stated above, and possibly others, users typically do not remove the detent 20 before using the syringe 10.

[0029] External sterilization of injection devices during the manufacturing and / or assembly process may be desirable and / or required by regulation. Additionally, some applications of prefilled syringes (such as certain ophthalmic applications) require external sterilization. For example, 21 CFR 200.50 indicates that "ophthalmic preparations and dispensers should be sterile." Furthermore, ANSI / AAMI ST67:2011 / (R)2017 provides "Sterilization of Health Care Products - Requirements and Guidance for Selecting a Sterility Assurance Level (SAL) for Products to be Labeled "Sterile"," where section 4.1.1 states that "SAL values ​​of 10-6 are generally used for terminal sterilization of health care products." Furthermore, Appendix A of ST67 and EN556-1:2006 states: "Sterilization of medical devices - Requirements for medical devices to be designated "sterile" - Part 1: Requirements for terminally sterilized medical devices"...Section 4.1: "For a terminally sterilized medical device to be designated "sterile", the theoretical probability of viable microorganisms being present on / in the device is greater than 1 x 10 -6 Therefore, the microbial contamination should be less than 1 x 10 -6 (For example, 1×10 -6 ) may be desirable and / or required.

[0030] Thus, the embodiments disclosed herein are particularly advantageous in these types of applications. As used herein, the terms "external sterilization" and / or "externally sterilizing" refer to a sterilization process of an injection device after it has been assembled. For example, the injection device shown in the figures may be externally sterilized after the syringe 10 (with drug in cavity 13), plunger rod 16, detent 20, and protective cap (not shown) are all assembled. During the external sterilization process, the injection device is typically placed in a sterilization chamber and exposed to a sterilizing gas such as ethylene oxide (EtO), nitrogen dioxide (NO2), vaporized hydrogen peroxide (VPHP), carbon dioxide (CO2), chlorine dioxide, or any other suitable gas for a predetermined length of time and other specified conditions (such as temperature and pressure). Then, after the sterilization cycle, the sterilizing gas is purged from the chamber and the injection device remains in the chamber (substantially or completely free of sterilizing gas) for another predetermined length of time and other specified conditions (such as temperature and pressure).

[0031] 2A-2H illustrate another exemplary detent 120 that may be used with a syringe 10 as shown in Figures 2A-2C. The detent 120 may generally include a collar portion 130 that extends around at least a portion of the syringe 10, an exterior gripping portion 140 for handling and / or gripping by a user, at least one protrusion such as a ridge 150 that helps to allow or promote air flow through a space between the detent and the syringe, a cavity 160 for receiving at least a portion of the syringe flange 12, and an opening 170 that allows the plunger rod 16 to extend through the detent 120.

[0032] The collar portion 130, as best seen in FIGS. 2D-2H, defines an inner surface 132 that extends around at least a portion of the syringe 10. As a more specific example, the inner surface 132 is a generally annular surface that extends around a majority of the circumference of the barrel 11 of the syringe 10. As an even more specific example, the inner surface 132 extends around a majority of the circumference of the distal portion 11c of the barrel 11, which portion is highlighted in FIGS. 13A-13C. In some forms, the "portion" of the circumference of the barrel 11 that is encompassed by the inner surface 132 can be a portion of the circumference of a region of the barrel 11, the entire circumference of a region of the barrel 11, or any other discrete area of ​​the surface of the barrel 11. The inner surface 132 can have generally the same curvature as the barrel 11 and can extend around the barrel 11 over the length of the inner surface 132. As shown in FIG. 2D , the inner surface 132 may extend on the inner surface of the collar 130 in a generally circular / annular manner except where the collar 130 and the inner surface 132 terminate over an opening 134 in the collar 130, which allows the detent 120 to couple with the syringe 10. As a more specific example, the opening 134 allows the detent 120 to receive the syringe 10 by sliding the syringe 10 toward (or away from) the detent 120 until the syringe 10 contacts the detent 120 in a snap-fit ​​configuration. As another example, the inner surface 132 extends approximately 270 degrees around the circumference of the barrel 11. The axial length of the collar 130 (measured along the axis of the barrel 11) is approximately 5 millimeters, but may have other suitable lengths. As the axial length of the collar 130 increases, the connection between the syringe 10 and the detent 120 may become more secure. Similarly, or alternatively, as the axial length of collar 130 increases, the center of gravity may be moved farther away from the midpoint of the axial length, making it easier to orient detents 120 during manufacturing. As a more specific example, it may be desirable to use a "shaker" or "feeder" receptacle, such as a pan or bowl, for automated assembly of syringes and to similarly orient multiple detent components in a shaking tray to simplify the manufacturing process.The feeder bowl may have, for example, a central receptacle with a spiral track along the receptacle's sidewall that carries the parts upward through the sidewall toward the receptacle's top edge (where the parts may be fed to an assembly station). Often, feeder bowls are more reliable and / or effective when the center of gravity of the components is at least some distance away from the midpoint of the axial length of the components, thereby flipping all or substantially all of the components toward the "heavier" side of the components. The center of gravity of the detent 120 is shown in FIG. 2F by reference numeral 136. Additionally, feeders are often more reliable when the parts have some asymmetrical features (along at least one or two axes), and the feeder has a track edge or pattern that can force improperly oriented parts back into the bowl. In this case, the track edge or pattern feature acts as a gate; that is, when the part is in the correct orientation, the part does not interact with the feature, but when the part is in the wrong orientation, the part interacts with the feature and falls back into the bowl.

[0033] As discussed above, the detent 120 provides a user with a larger gripping surface than the flange 12 of the syringe 10. As a more specific example, the flange portion 12 shown in Figures 2A and 2B has a generally elliptical or oval configuration with a maximum width 12a of about 13 millimeters and a barrel 11 diameter of about 9.5 millimeters. Thus, the flange portion 12 has an effective gripping surface of about 2 millimeters on each side of the flange portion 12. In comparison, the detent 120 has a maximum width 120a of about 34 millimeters and a collar width 130b (Figures 2D and 2H) of about 12 millimeters. Thus, the outer gripping portion 140 of the detent 120 has an effective gripping surface of about 11 millimeters on each side of the collar 130.

[0034] The external gripping portion 140 has an angle 142 (FIG. 2C) of approximately negative 25 degrees relative to the top surface 144 of the detent 120. Thus, the external gripping portion 140 has an angle of 115 degrees relative to the syringe axis 11d. It may be desirable for the angle of the external gripping portion 140 relative to the syringe axis 11d to be closer to 90 degrees (i.e., 135 degrees or less) than 180 degrees to allow the user to have an adequate grip on the external gripping portion 140. It may be more desirable for the external gripping portion 140 to have a smaller angle relative to the syringe axis 11d, such as 125 degrees or less, or 120 degrees or less, or 115 degrees or less. The external gripping portion 140 may also include anti-slip or grip enhancing features, such as ribs or a material with a relatively high coefficient of friction.

[0035] As discussed above, the detent 120 may also include at least one protrusion, such as at least one ridge 150, that engages the syringe 10 to move the collar inner surface 132 away from the syringe 10. As a more specific example, the detent inner surface 132 may include at least one protrusion 150 that extends away from the inner surface 132 and is configured to engage the flange 12 and / or the barrel 11 to allow or promote air flow through a space 152 between the inner surface 132 and the syringe 10. In FIGS. 2A-2H, the detent includes five ridges 150a, 150b, 150c, 150d, and 150e that are generally spaced apart from one another around the collar inner surface 132, and more preferably are generally equally spaced apart from one another to form a five-point engagement between the detent 120 and the syringe 10. However, any suitable ridges may be used, such as one, or two, or three, or four, or five, or six, or seven, or eight, or nine, or ten or more. The ridges 150 may be integrally formed with the collar inner surface 132 of the detent 120, or the ridges 150 may be separate components attached to the collar inner surface 132. In either case, the ridges 150 may cooperate to allow for a relatively secure fit between the detent 120 and the syringe 10 while providing a space 152 between the inner surface 132 and the syringe 10. For example, the ridges 150 may engage the barrel 11 in a snap-fit ​​relationship. Although the ridges 150a, 150b, 150c, 150d, and 150e shown in the figures are generally parallel to the syringe axis 11d, they may have other configurations. The ridges 150a, 150b, 150c, 150d and 150e shown in the figures may extend along the entire height 138 of the collar 130, as shown in FIG. 2E, or the ridges 150a, 150b, 150c, 150d and 150e may extend along only a portion of the height of the collar 130.

[0036] By allowing air flow through the space 152 (FIG. 2D) between the inner surface 132 and the syringe 10, the detent 120 and the syringe 10 cooperate to minimize or eliminate any occlusion areas between the collar inner surface 132 and the barrel or flange. For example, in one embodiment, the ridge 150 is only at the portion where the collar inner surface 132 engages the barrel 11.

[0037] Alternatively, the protrusions of the detents 120 shown in Figures 2A-2H may have any suitable configuration that allows air flow through the space 152 between the inner surface 132 and the syringe 10. For example, in one embodiment, the protrusions may be replaced with generally circular nubs, bumps, or other non-linear protrusions. As a more specific example, the protrusions of the detents 120 may have a shape and size similar to the nubs shown in Figures 4A and 4B, but may be disposed on the collar 130 instead of within the cavity.

[0038] As mentioned above, the detent 120 includes a cavity 160 for receiving at least a portion of the syringe flange 12. As a more specific example, the cavity is defined by opposing surfaces 162, 164 (FIGS. 2E and 2F). As shown in FIG. 2C, the distance between the opposing surfaces 162, 164 can be greater than the axial height of the flange 12 such that a gap 166 exists between at least one of the opposing surfaces 162, 164 and the upper and lower surfaces of the flange 12. As a more specific example, the gap 166 shown in FIG. 2C is between the lower opposing surface 162 and the lower surface of the flange 12, but in other configurations, a similar gap can exist between the upper opposing surface 164 and the top surface of the flange or on both sides (top and bottom) of the flange 12. The gap 166 and other similar gaps described herein may be advantageous to allow or encourage air flow and / or prevent or reduce occlusion spaces.

[0039] Cavity 160 is preferably shaped and sized to receive the entire flange 12 to promote a secure engagement between collar 130 and barrel 11. Cavity 160 may also be shaped and sized to receive flange 12 in any orientation to simplify and / or improve manufacturing. For example, cavity 160 may be shaped and sized to receive flange 12 having its maximum width in any orientation. As a more specific example, the minimum width of cavity 160 may be at least slightly greater than the maximum width of flange 12 such that the flange may be inserted in any orientation and / or the flange 12 may freely rotate within detent 120.

[0040] As discussed above, opening 170 allows plunger rod 16 to extend through detent 120. Opening 170 may be sized to allow free movement of plunger rod 16 except when locking ring 16a abuts or engages a surface defining opening 170. As a more specific example, opening 170 may have a diameter or width that is at least slightly larger than the diameter or width of the portion of the plunger rod designated by reference number 16 in FIG. 1 (i.e., the section of the plunger rod having a plus-shaped cross-section), but the diameter or width of opening 170 is at least slightly smaller than the diameter or width of locking ring 16a, thereby preventing or limiting plunger rod 16 from moving proximally beyond the point shown in FIG.

[0041] 3A-3B show another exemplary detent 220 that may be used with any suitable drug delivery device, for example, a syringe, such as the syringe 10 shown in the previous figures. The detent 220 may generally include a collar portion 230 that extends around at least a portion of the syringe 10, an external gripping portion 240 for handling and / or gripping by a user, at least one protrusion, such as a ridge 250 that helps to allow or promote airflow through the space between the detent and the syringe, a cavity 260 for receiving at least a portion of the syringe flange 12, and an opening 270 that allows the plunger rod 16 to extend through the detent 220. The detent 220 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing same, or other suitable features. Additionally, the detent 220 further includes at least one protrusion 255 that extends into the cavity 260. As a more specific example, the detent 220 includes a number of ridges 255a, 255b, 255c, and 255d that respectively engage, abut, and / or are disposed adjacent various portions of the flange 12 to direct or encourage air flow into the cavity 260. This configuration may avoid or minimize spaces or gaps between the upper and lower opposing surfaces that define the cavity 260, thereby potentially providing a more secure connection between the syringe 10 and the detent 220 while also minimizing or reducing trapped air spaces.

[0042] 4A-4B show another exemplary detent 320 that may be used with any suitable drug delivery device, for example, a syringe, such as the syringe 10 shown in the previous figures. The detent 320 may generally include a collar portion 330 that extends around at least a portion of the syringe 10, an external gripping portion 340 for handling and / or gripping by a user, at least one protrusion, such as a ridge 350 that helps to allow or promote airflow through a space between the detent and the syringe, a cavity 360 for receiving at least a portion of the syringe flange 12, and an opening 370 that allows the plunger rod 16 to extend through the detent 320. The detent 320 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing same, or other suitable features. Additionally, the detent 320 further includes at least one protrusion 355 that extends into the cavity 360. As a more specific example, the detent 320 includes a plurality of masses extending from opposing surfaces of the cavity. As an even more specific example, the detent 320 shown in Figures 4A-4B shows eight total masses, four pairs indicated by reference numbers 355a, 355b, 355c, and 355d. Each pair of masses engages, abuts, and / or is positioned adjacent to various portions of the flange 12 to pass or encourage air flow into the cavity 360. This configuration may avoid or minimize spaces or gaps between the upper and lower opposing surfaces that define the cavity 360, thereby potentially providing a more secure connection between the syringe 10 and the detent 320 while also minimizing or reducing trapped air spaces.

[0043] 5A-5E show another exemplary detent 420 that may be used with any suitable drug delivery device, for example, a syringe, such as the syringe 10 shown in the previous figures. The detent 420 may generally include a collar portion 430 that extends around at least a portion of the syringe 10, an external gripping portion 440 for handling and / or gripping by a user, at least one protrusion, such as a ridge 450 that helps to allow or promote airflow through the space between the detent and the syringe, a cavity 460 for receiving at least a portion of the syringe flange 12, and an opening 470 that allows the plunger rod 16 to extend through the detent 420. The detent 420 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing same, or other suitable features. The collar 430 shown in FIG. 5A has a height 438 (e.g., length along axis 11d) that is less than the collar height 138 shown in FIGS. 2A-2H. As discussed above, a higher collar height may have some advantages and a lower collar height may have other advantages, although both or either designs may be preferred. The center of gravity of the detent 420 is indicated in FIG. 5C by reference numeral 436. Similarly or alternatively, a lower collar height 138 may be advantageous for a user who prefers to grip the barrel rather than gripping the detent with their fingers, since a lower collar provides better access to the syringe barrel. As a more specific example, a user may prefer to grip the syringe by the barrel, such that the backs of the user's fingers engage the exterior gripping portion 440, rather than the fronts of the user's fingers engage the exterior gripping portion 440.

[0044] 6A-6E show another exemplary detent 520 that may be used with any suitable drug delivery device, for example a syringe, such as the syringe 10 shown in the previous figures. The detent 520 may generally include a collar portion 530 that extends around at least a portion of the syringe 10, an external gripping portion 540 for handling and / or gripping by a user, at least one protrusion, such as a ridge 550 that helps to allow or promote airflow through the space between the detent and the syringe, a cavity 560 for receiving at least a portion of the syringe flange 12, and an opening 570 that allows the plunger rod 16 to extend through the detent 520. The detent 520 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing it, or other suitable features. The center of gravity of the detent 520 is indicated in FIG. 6C by reference numeral 536. The external gripping portion 540 has an angle 542 of about minus 15 degrees with respect to the horizontal (i.e., a line perpendicular to the axis). Thus, the external gripping portion 540 has an angle of 105 degrees with respect to the syringe axis 11d. It may be desirable for the angle of the external gripping portion 540 with respect to the syringe axis 11d to be closer to 90 degrees (i.e., 135 degrees or less) than 180 degrees to allow the user to have an adequate grip on the external gripping portion 540. It may be more desirable for the external gripping portion 540 to have a smaller angle with respect to the syringe axis 11d, such as 125 degrees or less, or 120 degrees or less, or 115 degrees, or 105 degrees or less. The external gripping portion 540 may also include anti-slip or grip enhancing features, such as ribs or a material with a relatively high coefficient of friction. As shown in FIG. 6E, the detent 520 has a cutout 580 to reduce material costs and part weight.

[0045] FIG. 7A illustrates another exemplary detent 620 that may be used with any suitable drug delivery device, for example, a syringe, such as the syringe 10 illustrated in the previous figures. The detent 620 may generally include a collar portion 630 that extends around at least a portion of the syringe 10, an external gripping portion 640 for handling and / or gripping by a user, at least one protrusion, such as a ridge 650 that helps to allow or promote airflow through the space between the detent and the syringe, a cavity 660 for receiving at least a portion of the syringe flange 12, and an opening 670 that allows the plunger rod 16 to extend through the detent 620. The detent 620 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing same, or other suitable features. The center of gravity of the detent 620 is indicated in FIG. 7C by reference numeral 636. The external gripping portion 640 has an angle 642 of approximately minus 15 degrees with respect to the horizontal (i.e., a line perpendicular to the axis). Thus, the external gripping portion 640 has an angle of 105 degrees relative to the syringe axis 11d. It may be desirable for the angle of the external gripping portion 640 relative to the syringe axis 11d to be closer to 90 degrees (i.e., 135 degrees or less) than 180 degrees to allow the user to have an adequate grip on the external gripping portion 640. It may be more desirable for the external gripping portion 640 to have a smaller angle relative to the syringe axis 11d, such as 125 degrees or less, or 120 degrees or less, or 115 degrees, or 105 degrees or less. The external gripping portion 640 may also include anti-slip or grip enhancing features, such as ribs or a material with a relatively high coefficient of friction. As shown in FIG. 7E, the detent 620 has a cutout 680 to reduce material costs and part weight. The detent 620 may be similar to the detent 520 shown in FIGS. 6A-6E, except that the top surface has a more tapered profile, as shown at the corners and as indicated by reference number 682. A more tapered profile may be advantageous from an ergonomic standpoint, an aesthetic standpoint, a material cost standpoint, and / or a part weight standpoint. As a more specific example, the tapered profile of detent 620 may provide a greater sense of precision to the user.

[0046] 8A-8C show another exemplary detent 720 that may be used with any suitable drug delivery device, for example a syringe, such as syringe 10 shown in the previous figures. Detent 720 may be similar to detent 120 shown in Figures 2A-2H, except that outer gripping portion 740 has a more horizontal profile relative to the syringe axis. A more horizontal profile may be advantageous from a gripping standpoint.

[0047] 9A-9D show another exemplary detent 1020 that may be used with any suitable drug delivery device, for example a syringe, such as the syringe 10 shown in the previous figures. The detent 1020 may generally include a collar portion 1030 that extends around at least a portion of the syringe 10, an external gripping portion 1040 for handling and / or gripping by a user, at least one protrusion, such as a ridge 450, that helps to allow or promote airflow through the space between the detent and the syringe, a cavity 1060 for receiving at least a portion of the syringe flange 12, and an opening 1070 that allows the plunger rod 16 to extend through the detent 1020. The detent 1020 may include the features described in FIGS. 2A-2H and the corresponding paragraphs describing it, or other suitable features. The center of gravity of the detent 1020 is indicated in FIG. 9B by reference numeral 1036.

[0048] At least some of the detents shown in the figure were subjected to lethality testing. For example, the prefilled syringe was "spiked" with 1x10^6-6x10^6 CFU (e.g., 1,000,000-6,000,000 CFU) of Geobacillus stearothermophilus prior to the sterilization cycle. As a more specific example, the detents and barrel of the prefilled syringe were spiked with 1-6x10^6 CFU of Geobacillus stearothermophilus. As used herein, the term "CFU" refers to "colony forming units". "Colony forming units" are units used to estimate the number of viable bacterial or fungal cells in a sample ("viability" being the ability to grow by binary fission under controlled conditions). Geobacillus stearothermophilus (formerly Bacillus stearothermophilus) is a rod-shaped, Gram-positive bacterium and a member of the phylum Firmicutes. This bacterium is thermophilic and widely distributed in soils, hot springs, and marine sediments, and can cause food spoilage. Therefore, spiked pre-filled syringes were sterilized using various sterilization parameters to measure the lethality of the sterilization process and evaluate the Sterility Assurance Level (SAL). The pre-filled syringes were spiked or directly inoculated with biological indicators, as described in more detail below.

[0049] An exemplary method of assembling and externally sterilizing a drug delivery device according to an embodiment of the present disclosure will now be described. During a first step, at least some individual components of the drug delivery device are often sterilized before being received by a manufacturing facility. For example, the syringe barrel and plunger stopper as well as any other components that may be in direct contact with the drug product may be sterilized during this step. This step may use various techniques known to sterilize the various unassembled components of the drug delivery device, including but not limited to the components shown in the figures. During a second step, the barrel is filled and the stopper (also known as the "plunger stopper") is assembled with the barrel. The assembly step may also include adding at least some of the following: plunger rod, flange extender, tip cap with luer lock, needle, rigid needle shield and / or detent such as those shown in the figures. At least some of these components may be pre-assembled with each other, but they may also be assembled at the filling line, for example, when the filling process is performed aseptically. Also, syringes typically have either a tip cap luer lock tip or an attached (eg, fixed) needle, rather than having both components.

[0050] The external sterilization step then proceeds. First, the syringe is primed. In a process using nitrogen dioxide (NO2), the prime may include at least some or all of the following steps: removing the sample from storage, equilibrating the syringe at room temperature conditions for a desired amount of time (e.g., 30 minutes, 90 minutes, 2 hours, or any desired amount of time), and placing the syringe in a sterilization chamber. Prime may be performed inside or outside the chamber. When using ethylene oxide (EtO), the prime step may differ slightly from that described for NO2. For example, the syringe may be primed inside the sterilization chamber (without gas injection) for 360 minutes (or another desired length of time). However, similar to the process using NO2, the prime step using EtO may be performed inside or outside the chamber.

[0051] The sterilization chamber is then closed and all or substantially all of the air is evacuated from the chamber. The sterilization chamber is then humidified to a desired setting, such as 75 or 80 (or any desired amount of relative humidity percentage).

[0052] The desired sterilizing gas is then injected and held in the chamber for the desired dwell time. In a recipe using NO2, gas injection may include some or all of the following steps: delivering a dose of NO2 by drawing a vacuum in the chamber for a desired amount of time (i.e., dwell time) while injecting a desired amount of gas (dose concentration), purging the gas and releasing the vacuum, and then repeating these steps for a desired number of pulses. Once the desired number of pulses is completed, the gas is then finally purged and removed from the sterilization chamber. Finally, the chamber is vented (also known as "vent exchange") for a desired number of cycles to ensure that all or substantially all of the sterilizing gas is flushed from the syringe and package. The vacuum level may vary during these steps. For example, the vacuum during the dwell time may be a minimum, such as about 590 Torr.

[0053] The method may include any suitable parameters for the above steps, such as: The vacuum level may be about 100-500 Torr, about 150-400 Torr, about 150-300 Torr, or another suitable vacuum level. The NO2 dosage concentration can be about 2-20 milligrams per liter, about 2-10 milligrams per liter, about 2-7 milligrams per liter, or another suitable dosage concentration. The chamber may have a relative humidity of about 70 to 90 percent or another suitable humidity. The residence time may be about 2-20 minutes, about 2-12 minutes, about 2-7 minutes, or another suitable residence time. The number of pulses can be about 1-24, about 1-12, about 1-8, about 1-4, about 1-2 or another suitable number of pulses. The step of venting the sterilization chamber may include venting the sterilization chamber for about 12 to 35 cycles, or another suitable number of cycles.

[0054] As a more specific example, Table 1 shows different variables for ten different exemplary recipes for sterilizing drug delivery devices using nitrogen dioxide (NO2).

[0055] [Table 1]

[0056] As another example, Table 2 shows different variables for six different exemplary recipes for sterilizing a drug delivery device using NO2.

[0057] [Table 2]

[0058] In Tables 1 and 2, the labels in the "Vacuum Level (Torr)" column refer to the vacuum force applied to the external sterilization chamber during step 4 of FIG. 1. As shown, the vacuum force varies from 20 Torr to 500 Torr, although different vacuum forces may be appropriate. The listed vacuum force numbers are inverse to their strength, with a force of 20 Torr being stronger than a force of 100 Torr, which is stronger than a force of 500 Torr (atmospheric pressure is typically about 760 Torr). The stronger the vacuum force, the more likely it is to demonstrate kill of the desired bioburden. However, if the vacuum force becomes too high, the process may have undesirable effects on the drug, such as undesirably displacing the plunger (i.e., displacing it across the sterile barrier, causing a breach of sterility). The "NO2 Dose (mg / L)" column refers to the NO2 concentration (mg) per liter of air introduced into the external sterilization chamber. As shown, the doses in Tables 1 and 2 vary from 5-20 mg / L, although different doses may be appropriate. The higher the dose of NO2 during this process, the more quickly and more completely the drug delivery device will be sterilized. However, if the dose of sterilizing gas becomes too high, the process may have undesirable effects on the drug, such as contaminating the interior of the drug barrel with sterilizing gas (i.e., ingress of sterilizing gas and / or discoloration of syringe components). The "Relative Humidity (%RH)" column refers to the relative humidity in the external sterilization chamber. As shown, the relative humidity in each column of Tables 1 and 2 varies from 75%-80%, although different relative humidity values ​​may be appropriate. Increasing the relative humidity also increases the likelihood of demonstrating kill of the desired bioburden. The "Dwell Time (min:sec)" column refers to the amount of time the drug delivery device is in the sterilization chamber while sterilizing gas is present. For Tables 1 and 2, the "Total Dwell Time" is equal to the "Dwell Time" column multiplied by the "Number of Pulses" column. For example, for the first row in Table 1, the sample will have a total residence time of 80 minutes. As indicated, the residence times listed in Tables 1 and 2 vary from 5 to 20 minutes, although different residence times may be appropriate. Residence times also increase the likelihood of indicating destruction of the desired bioburden.However, if the residence time becomes too high, the process may have undesirable effects on the drug, such as contaminating the interior of the drug barrel with sterilizing gas. The "Number of Pulses" column refers to the number of times gas is injected by pulling a vacuum during the NO2 process. As shown, the pulses in each row of Tables 1 and 2 vary from 1 to 24, although different values ​​may be appropriate. The higher the pulse number, the more likely it is to demonstrate the kill of the desired microbial contaminant population. However, if the pulse number becomes too high, the process may have undesirable effects on the drug, such as contaminating the interior of the drug barrel with sterilizing gas. The column referring to "Number of Vents" refers to the number of times the chamber is vented after gas is purged from the chamber. Exemplary processes may use 12, 24, 28, 70 or any desired number of vent exchanges. Up to a point, by increasing the number of vents, the manufacturer can increase the likelihood that all or substantially all of the sterilizing gas is removed from the syringe and package (post-purge).

[0059] With respect to each recipe (NO2) in Table 1 and Figure 2, each step enclosed within Box 1 in Figure 1 may be carried out at room temperature (25 degrees Celsius), although other suitable temperatures may be used. However, other temperatures may be used, such as from about 2 degrees Celsius to about 8 degrees Celsius, or any other desired temperature that does not have an undesirable effect on the agent.

[0060] Table 3 shows the different variables of ten different exemplary recipes for sterilizing drug delivery devices using NO2.

[0061] [Table 3]

[0062] When using ethylene oxide (EtO), the gas injection process is slightly different. For example, the gas injection process may include some or all of the following steps: delivering a dose of EtO by drawing a vacuum in the chamber for a desired amount of time (i.e., residence time) while injecting a desired amount (dose concentration) of gas, and then purging the gas. In other words, when using EtO, it may be desirable to perform only one pulse rather than the preferred multiple pulses described above for NO2. For the gas purge venting step, an exemplary process using EtO proceeds as described above for NO2.

[0063] In particular, lethality tests of different detents, such as those disclosed herein, were conducted. Table 4 shows the results of lethality tests evaluating the effect of NO2-based sterilization on various pre-filled syringes with non-protruding and protruding detents.

[0064] [Table 4]

[0065] For each recipe number, five samples (or at least five test positions for one or more samples) were tested. Table 4 shows how many of the five samples reached the target lethality for each recipe in the "Detents Added" and "Barrel Added" columns. For example, the target lethality for this test was a Sterility Assurance Level (SAL) of 10^6. In other words, the target lethality for this test was a 6 log reduction in the number of bacteria present (pre-sterilization vs. post-sterilization). As a more specific example, for recipe number 1, for the detent region (row corresponding to recipe number 1 in the "Detents Added" column), one of the five samples tested reached this target lethality, but for the barrel region (row corresponding to recipe number 1 in the "Barrel Added" column), all five of the samples tested reached this target lethality. It should be noted that the test results of the added detents of recipes nos. 1-4 (using detents without protrusions) were tested by direct inoculation, while the test results of the added detents of recipes nos. 5-14 (using detents 120 or 220 shown in Figs. 3-4) were tested by biological indicators. Also, note that the "-" symbol indicates that no data is reported for these parameters / samples. Apart from the difference in test methodology, the samples tested with the detents with protrusions achieved a higher percentage of the target lethality compared to the samples with the detents without protrusions. As mentioned above, the ridges minimize and / or prevent occlusion spaces and instead allow the germicide to fully or substantially reach the various components of the prefilled syringe, especially the detent and flange areas.

[0066] Different sterilization parameters were also tested for intrusion studies. As mentioned above, it is desirable to achieve a target lethality during external sterilization, but it is also desirable to reduce, minimize and / or substantially prevent the intrusion of sterilization gas into the drug product chamber. However, the two goals (achieving lethality and minimizing intrusion) may be conflicting or offsetting concerns. For example, some sterilization parameters that can improve the likelihood of achieving a higher lethality rate may increase the likelihood of a higher intrusion of sterilization gas. Table 5 below shows the results of an intrusion study evaluating the effect of different recipes of NO2-based sterilization on the drug product chamber.

[0067] [Table 5]

[0068] The last four columns on the right (collectively labeled "NO2 Content in Product (PPM)") refer to the content of NO2 that invaded the drug product container, more specifically the content of NO2 that invaded the drug container, more specifically the NO2 levels measured as parts per million nitrate in the liquid. The first three columns in this group, labeled "Day 1," "Day 14," and "Day 30," refer to intrusion rates measured at different times after the sterilization process. The last column in this group, labeled "Control," refers to baseline levels of NO2 and the product of the sample (water for injection), nitrate (NO3). When compared to an "exposed" sample, such as Day 1, the control "unexposed" sample provides a baseline difference between the exposed sample and the control. For example, for Test No. 5, the intrusion rate on Day 1 is 0.342 and the control is 0.336, so the difference between the exposed and unexposed samples would be 0.006 PPM. Another potentially relevant parameter is that the test method may have an error rate of + / - 0.1 PPM.

[0069] In general, it may be desirable to minimize or substantially or completely prevent ingress, but to avoid exceeding an ingress amount of 3 PPM, 1 PPM, or another appropriate limit. It may be desirable to use "raw" 30-day values, such as those listed in the columns of Table 5 above, or "corrected" 30-day values ​​adjusted based on the control values. As shown in Table 5 above, nearly all ingress values ​​are below the 1 PPM threshold (the only exception is the 30-day measurement of sample 11). Also, as shown in Table 5 above, different vacuum powers, pulse numbers, and venting rate changes have different effects on ingress measurements. These parameters and trends may be utilized to determine sterilization parameters that achieve the target lethality while maintaining below the desired ingress level.

[0070] 10A-10C show a package 800 of an injection device according to another embodiment of the present disclosure. The package 800 includes a support wall 810 for receiving and supporting an injection device, such as the syringe 10 shown in the other figures. The package 800 can be used during various steps of the life cycle of the injection device, including during at least one or more of the following steps: external sterilization, shipping to a user, storage before use by a user, preparation of the injection device and injection site for use, and storage after injection. For example, at a manufacturing site, a manufacturer can place an assembled pre-filled syringe (e.g., syringe barrel, detent, stopper, plunger rod, drug, and protective cap) into the package such that the assembled pre-filled syringe is supported by the package 800 with a snap-fit ​​connection between the support wall 810 and the syringe barrel. The manufacturer can perform an external sterilization step on the assembled pre-filled syringe while the assembled pre-filled syringe is supported by the package 800. The manufacturer may then add a protective coating (not shown) onto the top wall 812 of the package to define a chamber 814 within the package 800 that forms an airtight seal and protects the assembled pre-filled syringe from outside air and / or contaminants. The protective coating may be a transparent plastic layer bonded to the package 800 by any suitable means, such as an adhesive and / or heat sealing process. During another step in the life cycle of the injection device, the user may peel off the protective coating to gain access to the pre-filled syringe.

[0071] The package 800 may include protrusions or spacers to limit surface area contact between the tray and the injection device, thereby reducing or preventing occlusion spaces therebetween. For example, the package 800 may include protrusions 820 that extend outwardly from the support wall 810 of the package 800 to create a gap between the injection device and the package 800, thereby minimizing or preventing occlusion spaces between the injection device and the package 800. The protrusions or spacers thereby allow an effective connection between the package and the injection device while allowing sterilization gas to flow between the components during the external sterilization step. The protrusions or spacers may also improve (reducing time and / or improving effectiveness) venting of sterilization gas after the external sterilization step. The package 800 shown in FIGS. 10A-10C includes two protrusions 820, although any suitable number may be used. Also, the protrusions 820 shown in FIGS. 10A-10C have a generally pyramidal shape, but may have any suitable shape. As another example, package 800 may not include a snap-fit ​​arrangement with the syringe, but instead may allow the syringe to rest within package 800 and allow sterilizing gas to flow between the components during an external sterilization step. In such a design, the gap between support walls 810 is larger than the diameter of the syringe to provide space between support walls 810 and the syringe. Also, in such a design, it is preferred that the Tyvek cover prevents the syringe from exiting the package.

[0072] The package 800 includes a hollow center section 840 (between the two snap-fit ​​areas 810) that is wider than other known center sections. For example, the distance 844 shown in FIG. 10C is preferably at least 1.5 centimeters to provide a user with space to grip the syringe 10 when removing it from the package 800. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 2.0 centimeters. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 2.5 centimeters. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 3.0 centimeters. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 4.0 centimeters. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 5.0 centimeters. Even more preferably, the distance 844 shown in FIG. 10C is preferably at least 6.0 centimeters.

[0073] FIG. 11 illustrates a package 900 for an injection device according to another embodiment of the present disclosure. For example, the package 900 includes a raised wall section 960. The raised wall section 960 is disposed near a portion of the package 900 that receives a plunger rod to secure the plunger rod of the injection device and / or prevent unintentional movement of the plunger of the injection device. For example, the package 900 illustrated in FIG. 11 includes a support wall 910 similar to that illustrated in FIGS. 10A-10C for receiving and supporting the barrel of the syringe 10. However, the package 900 shown in FIG. 11 also includes a raised wall section 960 having, for example, a side wall 960a for receiving and supporting the plunger rod 16 to receive the plunger rod end 14 and prevent and / or limit distal movement of the plunger rod end 14 (and the entire plunger rod 16) until the syringe 10 is removed from the package 900, and another wall 960c extending generally perpendicular to the support wall 910 and the side wall 960a.

[0074] It will be understood that the devices and methods according to the present disclosure may have one or more advantages over the prior art, any one or more of which may be present in a particular embodiment and in accordance with the features of the present disclosure included in that embodiment, and other advantages not specifically recited herein may be appreciated as well.

[0075] Preferably, the pre-filled syringe does not include an internal coating. The syringe may also include a coating on the exterior surface of the syringe that is in contact with the environment, such as an oxygen barrier coating.

[0076] The syringe barrel may have a length of 45-85 mm, 60-65 mm, or another suitable length. The length of the syringe barrel is the length between the rear end and the outlet where the needle is attached (but does not include the needle, if present).

[0077] The syringe barrel may have an internal diameter of 4 to 6.5 mm. If the syringe has a nominal maximum fill volume of 1 ml, the internal diameter of the syringe barrel may be 5.5 to 6.5 mm. If the syringe has a nominal maximum fill volume of 0.5 ml, the internal diameter of the syringe barrel may be 4 to 5 mm.

[0078] The wall of the syringe barrel may have a thickness of at least 1 mm, about 1-3 mm, about 1.5-3 mm, or about 2.4-2.8 mm. The wall thickness limits or prevents sterilizing gas from entering the interior of the syringe, thereby minimizing or preventing contact with the liquid formulation contained within the prefilled syringe.

[0079] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used with drugs, including, but not limited to, the drugs identified below and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may be used to refer to any type of pharmaceutical or therapeutic material, including conventional and non-conventional pharmaceuticals, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also included. Drugs may be in liquid form, lyophilized form, or reconstituted from lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0080] The drug is contained in a reservoir. Optionally, the reservoir is a prefilled syringe. The prefilled syringe may have a maximum filling volume, i.e., the volume that can be maximally occupied by the syringe, of 0.3 ml to 1.5 ml, preferably 0.5 ml to 1.0 ml. The amount of liquid composition filled into the syringe may be about 0.05 ml to 1.0 ml, about 0.1 ml to 0.5 ml, about 0.14 ml to 0.3 ml, or about 0.15 ml to 0.2 ml. The syringe is usually filled with an amount greater than the amount actually administered to the patient to allow for any dead space in the syringe and needle, as well as losses due to preparing the syringe for injection. Thus, the amount actually administered to the patient may be 0.01 ml to 1 ml, 0.02 to 0.5 ml, 0.025 to 0.5 ml, 0.03 ml to 0.05 ml, or 0.05 ml.

[0081] In some embodiments, the reservoir of the pre-filled syringe contains a VEGF inhibitor. For example, the VEGF inhibitor can be a non-antibody VEGF inhibitor. The term "VEGF inhibitor" refers to a molecule that specifically interacts with VEGF and inhibits one or more of its biological activities, such as its mitogenic activity, angiogenic activity, and / or vascular permeability activity. The VEGF inhibitor is intended to include both anti-VEGF antibodies and their antigen-binding fragments, and non-antibody VEGF inhibitors. Non-antibody VEGF inhibitors include aflibercept, pegaptanib, and antibody mimetics. The non-antibody VEGF inhibitor can be a VEGF trap. Preferably, the non-antibody VEGF inhibitor is aflibercept. Aflibercept, currently marketed under the name Eylea® and also known as VEGF Trap, is a recombinant human soluble VEGF receptor fusion protein in which portions of the extracellular domains of human VEGF receptors 1 and 2 are fused to the Fc portion of human IgG1 (Holash et al. (2002) Proc. Natl. Acad. Sci. USA 99(17):11393-11398, WO 00 / 75319 A1, U.S. Patent No. 7,070,959). Aflibercept contains Ig domain 2 of VEGFR1 and Ig domain 3 of VEGFR2 fused to the Fc domain of IgG1.

[0082] In some embodiments, the reservoir of the drug delivery device may be loaded with a colony stimulating factor such as granulocyte colony stimulating factor (G-CSF) or the device may be used in conjunction with a colony stimulating factor such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgastrim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF). In other embodiments, the drug delivery device may contain or be used in conjunction with an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates red blood cell production. In some embodiments, the ESA is an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs or derivatives thereof that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor.Erythropoiesis-stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), Epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin and molecules or variants or analogs thereof.

[0083] Among certain exemplary proteins are the specific proteins described below, including fusions, fragments, analogs, biosimilars, variants or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, peptibodies and related proteins, etc.; myostatin-binding proteins, including myostatin-specific peptibodies, peptibodies, related proteins, etc.; IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which in particular inhibit the activity mediated by binding of IL-4 and / or IL-13 to its receptor; interleukin-13 antibodies, peptibodies, related proteins, etc.; and IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which in particular inhibit the activity mediated by binding of IL-4 and / or IL-13 to its receptor. -Leukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, related proteins, etc.; Ang2 specific antibodies, peptibodies, related proteins, etc.; NGF specific antibodies, peptibodies, related proteins, etc.; CD22 specific antibodies, peptibodies, related proteins, etc., especially dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, such as the human CD22 of epratuzumab (CAS Registry Number 501423-23-0). human CD22-specific antibodies, such as, but not limited to, humanized and fully human monoclonal antibodies, including, but not limited to, human CD22-specific IgG antibodies, particularly including, but not limited to, bispecific fully humanized antibodies; IGF-1 receptor-specific antibodies, including, but not limited to, anti-IGF-1R antibodies, peptibodies and related proteins; B-7-related protein 1-specific antibodies, peptibodies, related proteins and the like (also referred to as "B7RP-1", B7H2, ICOSL, B7h and CD275), including, but not limited to, fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, including, but not limited to, a B7RP-specific fully human monoclonal IgG2 antibody, which inhibits the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1 on activated T cells; IL-15 specific antibodies, including, but not limited to, humanized monoclonal antibodies, peptibodies, related proteins, and the like; human IFNIFN gamma specific antibodies, peptibodies, related proteins, etc., including, but not limited to, fully human anti-IFN gamma antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., as well as other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; hepatocyte growth factor / scatter factor (HGF / SF):cMet axis (HGF / SF): such as fully human monoclonal antibodies that neutralize HGF / SF Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, etc., including those targeting HGF / SF:c-Met; TRAIL-R2 specific antibodies, peptibodies, related proteins, etc.; Activin A specific antibodies, peptibodies, related proteins, etc.; TGF-β specific antibodies, peptibodies, related proteins, etc.; Amyloid β protein specific antibodies, peptibodies, related proteins, etc.; proteins that bind to c-Kit and / or other stem cell factor receptors. c-Kit specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind OX40L and / or other ligands of the OX40 receptor; OX40L specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa or erythropoietin), GLP-1, Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon-beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-alpha4beta7mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Vectibix® (panitumumab), Xgeva ( (denosumab), Prolia® (denosumab), Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCimhR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP IL6 / IL6 receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20 mAb), Tarceva® (erlotinib), Roferon-A® (interferon alfa-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, an anti-α4 integrin mAb), Valortim® (MDX-1303, an anti-anthrax protective antigen mAb), ABthrax™, Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 Trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory proteins)), VEGF Trap (IgG1 Ig domain of VEGFR1 fused to Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβmAb(GC-1008), TRAIL-2 mAb(HGS-ETR2), TWEAK mAb, VEGFR / Flt-1 mAb, ZP3 mAb (HuMax-ZP3)

[0084] In some embodiments, the drug delivery device may house a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use, such as LUCENTIS® (ranibizumab). The drug delivery device may include a recombinant humanized monoclonal IgG1 antibody that includes human framework regions and mouse complementarity determining regions, such as AVASTIN® (bevacizumab). The drug delivery device may include a humanized monoclonal single chain Fv (scFv) antibody fragment, such as BEOVU® (brolucizumab-dbll), or may be used with a monoclonal antibody (IgG) that binds to sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, or BPS 804 / setrusumab (Mereo), and in other embodiments, human proprotein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9 specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including, but not limited to, OncoVEXGALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain or be used in conjunction with an endogenous tissue inhibitor of metalloproteinases (TIMP), such as, but not limited to, TIMP-3. Antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab and bispecific antibody molecules targeting the CGRP receptor as well as other headache targets, may also be delivered using the drug delivery device of the present disclosure.Additionally, bispecific T cell engaging (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), may be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery devices may contain or be used in conjunction with APJ large molecule agonists, such as, but not limited to, apelin or analogs thereof. In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibodies may be used in or with the drug delivery devices of the present disclosure.

[0085] Although the drug delivery devices, assemblies, components, subsystems and methods have been described in terms of exemplary embodiments, they are not limited to the exemplary embodiments. The detailed description should be construed as merely exemplary and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments would still fall within the scope of the claims that define the invention disclosed herein.

[0086] Those skilled in the art will understand that various modifications, alterations and combinations may be made to the above-described embodiments without departing from the spirit and scope of the present invention disclosed herein, and such modifications, alterations and combinations should be construed as being within the scope of the concept of the present invention.

Claims

1. 1. An injection device comprising: a syringe having a barrel and a flange; a detent configured to be coupled to the syringe adjacent the flange, the det having an inner surface generally extending around at least a portion of the syringe, the inner surface including at least one protrusion extending away from the inner surface and configured to engage the flange and / or the barrel to enable or promote air flow through a space between the inner surface and the syringe; an injection device comprising:

2. 2. The injection device of claim 1, wherein the detent includes at least two protrusions extending away from the inner surface and configured to engage the flange and / or the barrel to allow or promote air flow through the space between the inner surface and the syringe.

3. 3. The injection device of claim 2, wherein the detent includes at least three protrusions extending away from the inner surface and configured to engage the flange and / or the barrel to allow or promote air flow through the space between the inner surface and the syringe.

4. 4. The injection device of claim 3, wherein the detent includes at least four protrusions extending away from the inner surface and configured to engage the flange and / or the barrel to allow or promote air flow through the space between the inner surface and the syringe.

5. 5. The injection device of claim 4, wherein the detent includes at least five protrusions extending away from the inner surface and configured to engage the flange and / or the barrel to allow or promote air flow through the space between the inner surface and the syringe.

6. 6. The injection device of claim 5, wherein the detent includes at least seven protrusions extending away from the inner surface and configured to engage the flange and / or the barrel to allow or promote air flow through the space between the inner surface and the syringe.

7. An injection device according to any preceding claim, wherein the inner surface of the detent extends around at least a portion of the barrel of the syringe and the at least one protrusion engages the barrel of the syringe.

8. The injection device of any one of claims 1 to 7, wherein the detent includes a collar defining the inner surface generally extending around at least a portion of the barrel.

9. The injection device of claim 8 , wherein the collar is configured to engage the syringe in a snap-fit ​​relationship.

10. An injection device according to any preceding claim, wherein the syringe barrel defines an axis and the at least one protrusion is a rib extending generally parallel to the axis.

11. An injection device according to any preceding claim, wherein the detent defines a cavity for receiving at least a portion of the flange.

12. The injection device of claim 11 , wherein the detent includes opposing surfaces that define the cavity.

13. 13. The injection device of claim 12, wherein the inner surface of the detent includes the opposing surfaces that define the cavity, and the at least one protrusion extends away from at least one of the opposing surfaces.

14. 14. The injection device of claim 13, wherein the at least one protrusion includes at least one protrusion on an upper facing surface and at least one protrusion on a lower facing surface.

15. 15. The injection device of claim 14, wherein the at least one protrusion includes at least two ribs on the upper facing surface and at least two ribs on the lower facing surface.

16. 1. An injection device comprising: a syringe having a barrel; a package configured to receive and / or support the syringe, the package including a hollow surface and at least one protrusion extending away from the hollow surface, the at least one protrusion configured to engage the barrel of the syringe to allow or facilitate air flow through a space between the hollow surface and the syringe; an injection device comprising:

17. The injection device of claim 16, wherein the at least one protrusion comprises at least two protrusions.

18. The injection device of claim 17 , wherein the at least two protrusions are configured to engage the syringe in a snap-fit ​​relationship.

19. 1. An injection device comprising: a syringe having a barrel and a plunger rod at least partially received within the barrel; a package configured to receive and / or support the syringe, the package including a hollow surface, the hollow surface defining at least one stop surface configured to engage the barrel of the syringe and to prevent and / or limit movement of the plunger rod; an injection device comprising:

20. 20. The injection device of claim 19, wherein the package further comprises at least one protrusion extending away from the hollow surface, the at least one protrusion configured to engage the barrel of the syringe to allow or promote air flow through a space between the hollow surface and the syringe.

21. An injection device according to any one of claims 1 to 20, wherein the syringe is a pre-filled syringe containing a medicament.

22. 22. The infusion device of claim 21, wherein the drug comprises a VEGF inhibitor.

23. 23. The infusion device of claim 22, wherein the VEGF inhibitor comprises a non-antibody VEGF inhibitor.

24. 23. The infusion device of claim 22, wherein the VEGF inhibitor comprises a VEGF trap.

25. 25. The infusion device of claim 24, wherein the VEGF trap comprises aflibercept.

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