Syringe and method of assembly

Abstract

A syringe can include a container having a wall with an inner surface that defines a closed, sterile reservoir filled with a medical fluid or drug product. The syringe can also include a fluid delivery system that includes a sterile container needle that is in fluid communication with the container in a delivery state, but can or can not be in fluid communication with the container in a storage state. The sterile container needle is attached to a connector that is mechanically coupled to the container to secure the sterile container needle to the container with the needle in the storage state. Additionally, the syringe can include an actuator adapted to move the container needle from the storage state to the delivery state.

Description

[0001] Cross-references to related applications We claim priority to U.S. Provisional Application No. 61 / 895,390, filed October 24, 2013, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This patent relates to a syringe and a method of assembling the syringe, and specifically to a pre-filled syringe and a method of assembling the pre-filled syringe. Background Technology

[0003] A syringe is used to deliver medical fluids or pharmaceutical products (such as liquid medications) to a patient. Specifically, the syringe delivers fluid to the patient via a needle, cannula, or catheter that defines a flow path into the patient's body. Some syringes have a reservoir assembled by the manufacturer and pre-attached to the flow path. These reservoirs are typically provided empty by the manufacturer to the patient or healthcare provider (e.g., doctor, nurse, healthcare assistant, etc.) and then filled before use. Alternatively, the syringe may be used in combination with a pre-filled reservoir provided to the patient or healthcare provider.

[0004] In either case, the syringe must be prepared before use. For example, if the reservoir is provided empty, it must be filled. To do this, the syringe cartridge is filled with the medical fluid or drug product to be delivered, and then the medical fluid or drug product is injected into the reservoir through the inlet. Before injection, the inlet must be disinfected, for example, by wiping the outer surface with an alcohol wipe. Similarly, before connecting the pre-filled reservoir to the flow path in the alternative syringe, the mating connector must be disinfected by wiping the surface with an alcohol wipe.

[0005] In either case, the use of the syringe requires additional materials and time.

[0006] As described in more detail below, this disclosure provides an improved syringe that provides an advantageous alternative to the conventional apparatus and methods discussed above. Summary of the Invention

[0007] According to one aspect of this disclosure, a syringe includes a container, a sealing assembly, a fluid delivery system, and an actuator. The sealing assembly includes: a flexible sealing assembly wall having an inner surface, the container wall and the inner surface of the sealing assembly wall defining a closed sterile reservoir filled with a medical fluid or pharmaceutical product; and a barrier disposed outside the sealing assembly wall to define an enclosed space between the flexible wall and the barrier. The fluid delivery system includes a sterile container needle with a tip, the tip being positioned in a stored state to pass only through the barrier and in a delivery state to pass through the flexible wall into the sterile reservoir. The sterile container needle is attached to a connector mechanically coupled to the container to secure the sterile container needle to the container, wherein the needle is in the stored state. The actuator is adapted to move the container needle from the stored state to the delivery state.

[0008] According to another aspect of this disclosure, a method of assembling a syringe includes: filling a sterile reservoir of a container with a medical fluid or pharmaceutical product under sterile conditions, the reservoir being defined by an inner surface of the wall of the container; mechanically coupling a sterile fluid delivery system to the container under sterile conditions, the fluid delivery system being not in fluid communication with the reservoir in a storage state but in fluid communication with the reservoir in a delivery state; and assembling the remaining portion of the syringe under cleanroom conditions. Attached Figure Description

[0009] This disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may have been simplified by omitting selected elements in order to illustrate other elements more clearly. Such omissions of elements in some figures do not necessarily indicate the presence or absence of a particular element in any exemplary embodiment, except as may be explicitly stated in the corresponding written description. None of the figures are necessarily drawn to scale.

[0010] Figure 1 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, wherein the container needle is in a stored state, in which the needle partially pierces a single-piece wall of the container; Figure 2 Is with Figure 1 A perspective view of a syringe container used together to control the puncture of the container against the flexible monolithic wall of the container; Figure 3 yes Figure 1 A cross-sectional view of a syringe, wherein the container needle is in a delivery state, in which the needle pierces a single wall of the container, such that it is positioned to pass through the inner surface of the flexible wall into a sterile reservoir; Figure 4This is a schematic diagram of a manufacturing facility in which the syringe according to this disclosure can be filled and assembled; Figure 5 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, wherein the container needle is in a stored state, in which the needle partially pierces a single-piece wall of the container; Figure 6 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, wherein the container needle is in a stored state, in which the needle partially pierces a single-piece wall of the container; Figure 7 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, wherein the container needle is in a stored state, in which the needle partially pierces the barrier of the sealing assembly rather than the flexible wall; Figure 8 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, wherein the container needle is in a stored state, in which the needle partially pierces the barrier of the sealing assembly rather than the flexible wall; Figure 9 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, the syringe including a vent for evacuating the space between a flexible wall and an externally disposed barrier as the associated container needle moves between a storage state and a delivery state; Figure 10 This is a cross-sectional view of an embodiment of a syringe according to the present disclosure, the syringe including a bypass for evacuating the space between a flexible wall and an externally disposed barrier as the associated container needle moves between a storage state and a delivery state; Figure 11 yes Figure 10 A cross-sectional view of a container in an intermediate state, wherein the bypass is in fluid communication with the space defined between the flexible wall and the barrier; Figure 12 This is a cross-sectional view of a syringe according to an embodiment of the present disclosure, wherein sterile conditions are maintained in the reservoir until the fluid delivery system is actuated; Figure 13 This is a cross-sectional view of a syringe according to an embodiment of the present disclosure, wherein sterile conditions are maintained in the reservoir until the fluid delivery system is actuated; Figure 14 This is a cross-sectional view of a syringe according to an embodiment of the present disclosure, wherein sterile conditions are maintained in the reservoir until the fluid delivery system is actuated; Figure 15 This is a flowchart illustrating a method for assembling a syringe according to the present disclosure; Figure 16 This is a cross-sectional view of an embodiment of the syringe according to the present disclosure before assembly; Figure 17yes Figure 16 A cross-sectional view of an embodiment of a syringe, wherein the container needle is in a stored state, in which the needle partially pierces the barrier of the sealing assembly rather than the flexible wall; Figure 18 yes Figure 16 A cross-sectional view of an embodiment of a syringe, wherein the container needle is in a delivery state, in which the needle pierces the barrier and flexible wall of the sealing assembly; Figure 19 It is used with and Figures 16 to 18 The embodiment shown is a container pin and a container-like connector used together with a container; Figure 20 It is used with Figures 16 to 18 An embodiment of a connector shown that is used together with a container pin and a container; Figure 21 It is used with and Figures 16 to 18 The embodiment shown is a container pin and a container-like connector used together with a container; Figure 22 It is used with and Figures 16 to 18 The embodiment shown is a container pin and a container-like connector used together with a container; Figure 23 This is a flowchart illustrating a method for assembling a syringe according to the present disclosure; and Figure 24 yes Figure 16 A cross-sectional view of an embodiment of a syringe, wherein the container needle is in a stored state, in which the needle partially pierces the flexible wall of the sealing assembly. Detailed Implementation

[0011] While the following text sets forth a detailed description of various embodiments of the invention, it should be understood that the legal scope of the invention is defined by the language of the claims set forth at the beginning of this patent. It should also be understood that unless a term is explicitly defined in this patent using the sentence “As used herein, the term '______' is hereby defined as…” or a similar sentence, there is no intention to limit the meaning of such a term (explicitly or implicitly) beyond its ordinary or general meaning, and such terms should not be construed as being limited based on any statement made in any section of this patent (rather than the language of the claims). In the event that any term set forth in the claims at the beginning of this patent is referenced in this patent in a manner consistent with a single meaning, this is done solely for clarity and to avoid confusing the reader, and it is not intended that such claim terms be limited (implicitly or otherwise) to the single meaning stated. Furthermore, unless a claim element is defined by the descriptive terms “component” and “function” without describing any structure, it is not intended that the scope of any claim element be interpreted based on the application of paragraph 6 of 35 U.S.SC §112.

[0012] The detailed description is to be understood as exemplary only and does not describe every possible embodiment of the invention. Numerous alternative embodiments may be implemented using current technology or technology developed after the filing date of this patent, and these alternative embodiments will still fall within the scope of the claims defining the invention.

[0013] Generally, a syringe according to this disclosure comprises a container, a fluid delivery system, and an actuator. While the term "syringe" may refer in some cases to a delivery device that ensures the delivery of a fixed volume of medical fluid or pharmaceutical product, it will be understood that this disclosure also covers infusion devices, which in some cases may refer to a delivery device that ensures a specific delivery rate. As used herein, the terms medical fluid and pharmaceutical product may have the same or different meanings. The term medical fluid may encompass pharmaceutical products as well as other patient-deliverable substances. It should also be understood that the terms syringe and infusion device may be used interchangeably when referring to embodiments in this specification. Furthermore, the subassemblies of the container and fluid delivery system may be handled separately from the remainder of the syringe, whether such subassemblies are filled or unfilled with medical fluid or pharmaceutical product; for example, such subassemblies may be delivered as a unit during the assembly process in the manufacture of the syringe.

[0014] like Figures 1 to 3 and Figures 5 to 11As shown, the container may include a wall having an inner surface and a sealing assembly having an inner surface, the inner surfaces of which define a closed sterile reservoir filled with a medical fluid or pharmaceutical product. Furthermore, the fluid delivery system shown in these embodiments may include a sterile container needle, which may also be unshielded, having a needle tip positioned in a storage state to partially pass through the sealing assembly and in a delivery state to pass through the inner surface of the sealing assembly into the sterile reservoir. Thus, the needle is in fluid communication with the container in the delivery state but not in the storage state. According to these embodiments, the syringe may include an actuator adapted to move the container needle from a storage state to a delivery state, the movement potentially involving movement of the needle relative to the container or the container relative to the needle.

[0015] like Figure 1 , Figure 3 and Figures 4 to 6 As shown, the sealing assembly can be a flexible monolithic wall with an inner surface that defines the inner surface of the sealing assembly, and the tip of the container needle can be partially disposed within the monolithic wall. Alternatively, as... Figures 7 to 11 As shown, the sealing assembly may include: a flexible wall having an inner surface that defines an inner surface of the sealing assembly; and a barrier disposed outside the flexible wall to define an enclosure space between the flexible wall and the barrier. According to such an embodiment, in a storage state, the tip of a container needle is positioned to pass through the barrier into the space.

[0016] An embodiment of the syringe 100 according to this disclosure is shown in Figure 1 The syringe 100 includes a container 102, a fluid delivery system 104, and an actuator 106.

[0017] Container 102 (which may also be referred to as a cartridge) includes a wall 110 having an inner surface 112 and an outer surface 114. Although in Figure 1 The diagram shows a monolithic (i.e., one-piece) wall 110 defining both the inner surface 112 and the outer surface 114, but in other embodiments, the wall 110 may comprise multiple layers having different layers defining the inner surface 112 and the outer surface 114.

[0018] According to certain embodiments of this disclosure, wall 110 is rigid. In other embodiments, wall 110 is flexible due to the material defining the wall or the wall's structure (e.g., a bellows construction). Wall 110 may be made of, for example, glass, metal, or a polymer. Specifically, polymer versions may be made of, for example, polycarbonate, polypropylene, polyethylene (e.g., high-density polyethylene), polytetrafluoroethylene, cyclic olefin polymers, cyclic olefin copolymers, Crystal Zenith, etc. ®It can be made of olefin polymers (available from Daikyo Seiko Ltd., Japan), nylon, or engineering resins. As for the flexible version of wall 110, butyl rubber, silicone rubber, latex-based rubber, coated rubber, and multilayer polymer films can be used, such as those containing polyethylene (e.g., low-density polyethylene) and polypropylene.

[0019] The wall 110 may have a generally cylindrical shape, wherein a shoulder 120 separates a first cylindrical segment 122 having a first cross-sectional diameter from a second cylindrical segment 124 having a second cross-sectional diameter, the first cross-sectional diameter being smaller than the second cross-sectional diameter. The wall 110 may also define two opposing open ends 126, 128. The inner surface 112 of the wall 110, or more specifically, the wall 110, may also define a borehole 130.

[0020] In some embodiments, container 102 may include a flexible monolithic wall 140 having an inner surface 142 and an outer surface 144 (the wall may also be referred to as a seal or spacer). Wall 140 may be disposed in and fixedly attached to wall 110 of container 102 within a first open end 126 defined by wall 110, such that there is limited relative movement between wall 140 and wall 110, for example at the attachment point of wall 140 to wall 110 across the open end or opening 126. The inner surfaces 112, 142 of wall 110 and flexible wall 140 may at least partially define a closed sterile reservoir 150 filled with medical fluid or pharmaceutical product 160, which is described in more detail below. Wall 140 may be made of, for example, butyl bromide, butyl chloride or chlorobromobutyl rubber, fluoropolymer rubber, natural rubber, silicone rubber, silicone or salvaphine.

[0021] Container 102 may also include a stop or piston 170 having an inner surface 172 and an outer surface 174. The piston 170 may be received within an end 128 defined by wall 110 and may be movable along a bore 130 between ends 126, 128 of container 102. According to such embodiments, a reservoir 150 containing a medical fluid or pharmaceutical product 160 may be defined by walls 110, 140 and the inner surfaces 112, 142, 172 of piston 170.

[0022] Container 102 can be used in conjunction with fluid delivery system 104, the relevant portions of which are shown in Figure 1 Specifically, the fluid delivery system 104 may include a container needle 180 with a needle tip 182. As shown, the needle tip 182 is only partially disposed within the flexible wall 140 in the storage state. Puncture of the needle tip 182 into the wall 140 can be controlled by a variety of methods and / or mechanisms. For example, Figure 2A clamp is shown that can be used in combination with container 102 to control the depth to which needle 182 pierces wall 140.

[0023] The fluid delivery system 104 may also include an injection needle 190 having a tip 192. The tip 192 of the injection needle 190 may be covered with a needle shield 194 to prevent contact with and contamination of the tip 192. The container needle 180 and the injection needle 190 may be connected via a cannula or tube 200, which, according to some embodiments of this disclosure, may be a flexible cannula. Similar to the needle 180, the needle 190 may be made of, for example, stainless steel. In some embodiments, the container needle 180 and the injection needle 190 may be integrally formed (i.e., as a single piece).

[0024] The fluid delivery system 104 can be combined with Figure 1 The actuator 106 shown is used for this purpose. The actuator 106 can be adapted to cause the container needle 180 to... Figure 1 The storage state shown is the same as Figure 3 The fluid delivery system 104 moves between the delivery states shown and thus between the storage and delivery states. In the delivery state, the container needle 180 is positioned to pass through the inner surface 142 of the flexible wall 140 into the sterile reservoir 150 and to be in fluid communication with the reservoir 150.

[0025] The movement of needle 180 between the states can occur in various ways. For example, needle 180 may remain fixed relative to the housing of syringe 100, while container 102 may move relative to needle 180 and the housing. Alternatively, container 102 may remain fixed relative to the housing, while needle 180 may move relative to container 102 and the housing. In other embodiments, both container 102 and needle 180 move relative to the housing of syringe 100. It will be understood that all these actions are contained within the statement that actuator 106 is adapted to move container needle 180 between a storage state and a delivery state.

[0026] Actuator 106 can be mechanical, electromechanical, or electrical. For example, actuator 106 may include a solenoid, a motor-driven lever, a motor with associated transmission, etc. In some embodiments, a tab or button attached to container 102 or needle 180 allows a user to manually achieve relative movement between container 102 and needle 180. Container 102 may be housed within the tab or button, which is pressed into the housing when syringe 100 is activated to move container 102 relative to (fixed) needle 180.

[0027] Actuator 106 can move container needle 180 between a storage state and a delivery state by moving needle 180 from a storage state to a delivery state or by moving needle 180 from a delivery state to a storage state. In some embodiments, the actuator can repeatedly (i.e., multiple times or iteratively) move container needle 180 between the storage state and the delivery state. Actuator 106 can move container needle 180 immediately upon receiving an input or signal (e.g., generated by the depressing or actuation of a button, switch, or other input device coupled to actuator 106, which may be mechanical, electromechanical, or electrical in nature), or it can delay the movement of container needle 180 between the storage state and the delivery state for a period of time after receiving an input. According to a particular embodiment, actuator 106 can delay the movement of needle 180 from the storage state to the delivery state until after such a time delay.

[0028] According to embodiments of this disclosure, both the reservoir 150 and the container needle 180 (and any attached tubing 200 and injection needle 190) are described as sterile, while the remainder of the delivery device / syringe 100 (e.g., actuator 106) is described as clean. These terms describe the conditions resulting from the assembly of the reservoir 150, needle 180, or the remainder of the delivery device under conditions that will ensure a specified level of contamination-free status, wherein a sterile object or device is understood to have a relatively high level of contamination-free status compared to a clean object or device. As a non-limiting example, see [reference needed]. Figure 4 The concepts of sterility and cleanliness are discussed here, and this discussion applies to all embodiments described herein.

[0029] Figure 4 Manufacturing facility 250 is shown and can be used to discuss manufacturing processes carried out within facility 250. It will be noted that facility 250 is divided into multiple spaces 252, 254, 256, 258, 260, 262, 264, 266, and 268, which can be maintained by using permanent or semi-permanent walls or other barriers. It will be understood that some spaces or areas may not be divided by barriers or walls, but can instead be separated only at the organizational level. Furthermore, more or fewer spaces or alternative arrangements of said spaces can be used, and such different numbers or arrangements of spaces can be readily determined by those skilled in the art.

[0030] In some embodiments, components of container 102 (walls 110, 140 and stop / piston 170) and fluid delivery system 104 enter facility 250 through space 252, wherein said components are sterilized, for example, using electron beam technology. Alternatively, although referenced Figure 1 and Figure 3The embodiments define container 102 and fluid delivery system 104 as separate structures; however, it is well known that the manufacturing process described herein is used for a product in which container 102 is attached to fluid delivery system 104 (e.g., container 102 / fluid delivery system 104 is a syringe) before being introduced into space 254; and the product is sterilized. In some embodiments, as the components enter facility 250 at inlet points 252, 264, 266, the components can be sterilized by other currently known sterilization procedures (e.g., treatment with chlorine dioxide or gaseous hydrogen peroxide) or by sterilization procedures developed subsequently. Container 102 and fluid delivery system 104 are then passed into space 254 for filling with medical fluids or pharmaceutical products. Space 254 can be operated as a sterile Class 100 cleanroom. A Class 100 cleanroom is a cleanroom in which the number of particles of size 0.5 µm or larger per cubic foot of air is less than 100. Once filling has been performed and the stop 170 has been positioned in the end 128 of container 102, the container needle 180 is partially inserted into the wall / septum 140. Because the container needle 180 does not penetrate the wall 140, the reservoir 150 and the medical fluid or pharmaceutical product 160 remain sterile (i.e., at a high level of cleanliness). Furthermore, because the fluid delivery system 104 is sterile and assembled to container 102 under aseptic conditions, the fluid delivery system 104 is considered to remain sterile, partly due to the partial insertion of the container needle 180 and partly due to the shield 194.

[0031] A pre-filled container 102, combined with the associated fluid delivery system 104 (this combination may be referred to as a pre-filled sterile container assembly, or in those embodiments where the fluid delivery system 104 and container 102 are integrally attached to or formed (e.g., syringes) with each other, and the container 102 and fluid delivery system 104 may also be referred to as a pre-filled sterile syringe), is moved through a transfer space 256 (also operated as a Class 100 cleanroom, in some embodiments of which are also sterile) before being housed in storage space 258. The pre-filled sterile container assembly is moved from storage space 258 to inspection area 260 (sterile in some embodiments), where the pre-filled sterile container assembly is inspected before being assembled with actuator 106 and other components of syringe 100. Because the medical fluid or pharmaceutical product 160 is contained within the sealed container 102 and the fluid delivery system 104 remains sterile at this time (i.e., the container needle 180 is inserted into the wall 140 and the syringe needle 190 is covered by a shield 194), the inspection area can be operated as a Class 10,000 cleanroom. Once the inspection is complete, the pre-filled sterile container assembly can be transferred from the inspection space 260 to the assembly space 262.

[0032] Similar to inspection space 260, assembly space 262 can operate as a sterile Class 10,000 cleanroom, or in some embodiments as a Class 100,000 cleanroom. Materials transferred from spaces 264, 266 into the cleanroom can be under sterile conditions, or can be sterilized, for example, using electron beam technology. Within assembly space 262, the remaining portion of syringe 100 (e.g., actuator 106) can be assembled (i.e., the container 102 and fluid delivery system 104 can be housed within the remaining portion of syringe 100) before being transferred to packaging space 268.

[0033] Besides assembly, other processing may occur at this time. According to some embodiments, it may be desirable to arrange the fluid delivery system 104 in a configuration to facilitate delivery, for example, before assembly with the remainder of syringe 100, but to arrange it differently after assembly into syringe 100. For example, it may be desirable for the fluid path between container needle 180 and syringe needle 190 to be in a straight configuration before assembly with the remainder of syringe 100, but in a curved, bent (e.g., 60 degrees, 90 degrees, etc.) or other non-straight configuration when assembled with the remainder of syringe 100. By maintaining the fluid delivery system 104 in a straight configuration, the spacing of the pre-filled sterile container assembly in the tray or other holder for delivering the pre-filled sterile container assembly can be maximized, as the additional space required to accommodate curved, bent, or other non-straight configurations can be avoided. This may also affect the cost of filling container 102, as each tray can accommodate a large number of container 102 / fluid delivery system 104 assemblies, and therefore the number of trays that can be passed through space 254 may be limited. Configuration changes can be made in assembly space 262, for example, to minimize the need to house the curved, bent, or otherwise non-pen DC delivery system 104 elsewhere in facility 250.

[0034] Figure 1 and Figure 3 The embodiment of the syringe 100 shown is exemplary. Figure 5 and Figure 6 Show Figure 1 and Figure 3 The syringe shown is a variant.

[0035] according to Figure 5 In one embodiment, the syringe 300 includes a container 302, a fluid delivery device 304, and an actuator 306. (Compared to...) Figure 1 and Figure 3Similar to the embodiments, container 302 includes a wall 310 having an inner surface 312 and an outer surface 314. The wall 310 may have two opposing ends 320, 322, wherein the inner surface 312 of the wall 310 defines a borehole 324 between the opposing ends 320, 322.

[0036] Unlike container 102, container 302 has a fixed plug 326 that closes end 320. Additionally, although container 302 has a flexible monolithic wall 330 with an inner surface 332 and an outer surface 334, the wall 330 is positioned within end 322 of container 302 and thus functions as a stop / piston 170 in container 102. Therefore, wall 330 is movable along borehole 324 between opposing ends 320, 322. The inner surfaces 312, 332 of walls 310, 330 define a sterile reservoir 340 in which a medical fluid or pharmaceutical product 350 is disposed.

[0037] The fluid delivery device 304 may include a sterile container needle 360 ​​with a needle tip 362. Similar to the needle tip 182 of needle 180, the needle tip 362 of needle 360 ​​is only partially housed within a flexible wall 330 in a storage state, wherein an actuator 306 causes the needle tip 362 to move between a storage state and a delivery state, in which the needle tip 362 is positioned to enter a sterile reservoir 340 through the inner surface 332 of the flexible wall 330. The container needle 360 ​​may, for example, be in fluid communication with an injection needle 370 having a needle tip 372 covered by a sheath 374 via a sleeve 380, the sleeve being housed within a piston rod 382, ​​which can be used to move a stop / piston 330 between the ends 320, 322 of the container 302.

[0038] according to Figure 6 In the embodiment shown, the container has a wall 390 having an inner surface 392 and an outer surface 394. Unlike the containers previously discussed, the wall 390 defines a closed end 396 and an open end 398. The container also includes a flexible wall 400, which... Figure 5 Similar to wall 330 in the embodiment, wall 400 is movable within the container between open end 398 and closed end 396. According to this embodiment, a separate structure is not required to seal one of ends 396, 398, because wall 390 itself defines closed end 396. Closed end 396 can be resized such that it is radially larger than... Figure 6 The one shown in the image.

[0039] In the context of the several embodiments already discussed in which the sealing assembly comprises only a flexible monolithic wall, see [link to previous text]. Figures 7 to 11 Several other embodiments are discussed, in which the sealing assembly comprises multiple walls and / or seals. This structure may be referred to as a partition seal (or, as seen in [reference]). Figure 7 The partition, or for reference Figures 8 to 11 (The barriers). Although these walls and / or seals may be shown and referred to as walls and barriers, it will be appreciated that these structures may be defined as part of a single structure (e.g., a single septum with a central space).

[0040] See Figure 7 The syringe 450 includes a container 452, a fluid delivery system 454, and an actuator 456.

[0041] Container 452 includes a wall 460 having an inner surface 462 and an outer surface 464. Figure 1 and Figure 2 Similar to the container, wall 460 may have a generally cylindrical shape, wherein shoulder 470 separates a first cylindrical segment 472 having a first cross-sectional diameter from a second cylindrical segment 474 having a second cross-sectional diameter, the first cross-sectional diameter being smaller than the second cross-sectional diameter. Wall 460 may also define two opposing open ends 476, 478. The inner surface 462 of wall 460, or more specifically wall 460, may also define a borehole 480.

[0042] and Figure 1 and Figure 3 The container 102 is different. Figure 7 Container 452 has a sealing assembly comprising more than one single wall. The sealing assembly of container 452 includes a flexible wall 490 and a barrier 492. The flexible wall 490 has an inner surface 494 and an outer surface 496, while the barrier 492 has an inner surface 498 and an outer surface 500. The inner surfaces 462 and 494 of wall 460 and flexible wall 490 define a closed sterile reservoir 510 to be filled with medical fluid or pharmaceutical product 520. In some embodiments, barrier 492 is disposed outside flexible wall 490 to define an enclosed space 530 between flexible wall 490 and barrier 492. Space 530 may be defined by the inner surface 462 of wall 460, the outer surface 496 of flexible wall 490, and the inner surface 498 of barrier 492.

[0043] Container 452 may also include a stop or piston 540 having an inner surface 542 and an outer surface 544. The piston 540 may be housed within an end 478 defined by wall 460 and may be movable along a bore 480 between ends 476, 478 of container 452. According to such embodiments, a reservoir 510 containing a medical fluid or pharmaceutical product 520 may be defined by walls 460, 490 and the inner surfaces 462, 494, 542 of piston 540.

[0044] Figure 7Embodiments also include a fluid delivery system 454 comprising a sterile container needle 550 having a needle tip 552, the needle being positioned in a storage state to penetrate a barrier 492 into a space 530 and in a delivery state to penetrate the inner surface 494 of a flexible wall 490 into a sterile reservoir 510. The container needle 550 only partially punctures the sealing assembly. The fluid delivery system 454 may also include an injection needle 560 having a needle tip 562, the needle being at least initially covered by a needle shield 564 to prevent contact with and contamination of the needle tip 562. The container needle 550 and the injection needle 560 may be connected via a cannula or tube 570, which, according to some embodiments of the present disclosure, may be a flexible cannula.

[0045] like Figure 8 As shown, the sealing assembly of syringe 600 is disposed in container 602, replacing the stop / piston 540 described with respect to container 452. That is, container 602 includes a wall 604 defining a borehole 606, and a flexible wall 608 and a barrier 610 each define a stop movable along the borehole 606. Although in the illustrated embodiment the wall 604 of container 602 does not define opposing open and closed ends, such alternatives are possible.

[0046] Figures 9 to 11 Show Figure 8 Variations of the embodiments shown include additional features to allow evacuation or venting of the space or area between the flexible wall and the barrier. These additional features may be referred to as vents, valves, or bypasses, but all of these structures allow gas to escape from the space or area between the flexible wall and the barrier when the actuator moves the associated container needle from a storage state to a delivery state. According to other embodiments of this disclosure, this does not indicate that the inner wall and outer barrier cannot be kept separate, for example, by using one or more spacers. Figures 9 to 11 The illustrated embodiment shows an option for evacuating the space, wherein the inner walls and outer barriers converge. It will be understood that vents, valves, and bypasses will maintain sterile conditions within the space until the space is evacuated or drained.

[0047] Figure 9The diagram shows a container 650 comprising a wall 652 and a sealing assembly, the assembly including a flexible wall 654 and a barrier 656. The flexible wall 654 has an inner surface 658 and an outer surface 660, while the barrier 654 has an inner surface 662 and an outer surface 664. The inner surface 668 of the wall 652 and the inner surface 658 of the flexible wall 654 define a closed, sterile reservoir 670 to be filled with a medical fluid or pharmaceutical product 680. The barrier 656 is disposed outside the flexible wall 654 to define an enclosed space 690 between the flexible wall 654 and the barrier 656. The space 690 may be defined by the inner surface 668 of the wall 652, the outer surface 660 of the flexible wall 652, and the inner surface 662 of the barrier 656.

[0048] like Figure 10 As shown, a fluid delivery system 700, including a container needle 702, is used in conjunction with the sealing assembly. The container needle 702 is shown in a storage state. The container needle 702 is positioned through a barrier 656, such that the needle tip 704 of the needle 702 is positioned in a space 690. In the delivery state (not shown), the needle tip 704 will pierce the flexible wall 654 and extend into the reservoir 670. The needle 702 is not drawn to scale, particularly regarding its length.

[0049] Figure 9 The container 650 shown includes at least one vent 710. The vent 710 is in fluid communication with a space 690 between a barrier 656 and a flexible wall 654. The vent 710 is selectively actuated to allow gas trapped between the barrier 656 and the flexible wall 654 to escape through the vent 710 as the sealing assembly moves between the shown storage and delivery states, wherein the barrier 656 advances in the direction of the flexible wall 654 to allow the needle 704 of the container needle 702 to penetrate the wall 654. In some embodiments, the vent 710 may be sealed relative to the environment until, for example, it is actuated by a pressure change within the space 690.

[0050] A vent 710 is disposed within a barrier 656 and extends between the inner surface 662 and the outer surface 664 of the barrier 656. A fin 712 covers the end of the vent 710 near the outer surface 664, thereby sealing the end of the vent 710 until the vent is actuated, thus maintaining the sterility of the space 690 between the barrier 656 and the flexible wall 654. Alternatively, the vent 710 may be arranged, for example, in the wall 652 of the container 650.

[0051] Figure 10 and Figure 11 Show Figure 8Another variation of the system includes a container 720 comprising a wall 722 and a sealing assembly comprising a flexible wall 724 and a barrier 726. The flexible wall 724 has an inner surface 728 and an outer surface 730, while the barrier 726 has an inner surface 732 and an outer surface 734. The inner surface 738 of the wall 722 and the inner surface 728 of the flexible wall 724 define a closed, sterile reservoir 740 to be filled with a medical fluid or pharmaceutical product 750. The barrier 726 is positioned outside the flexible wall 724 to define an enclosed space 760 between the flexible wall 724 and the barrier 726. The space 760 may be defined by the inner surface 738 of the wall 722, the outer surface 730 of the flexible wall 722, and the inner surface 732 of the barrier 726.

[0052] like Figure 10 As shown, a fluid delivery system 770 comprising a container needle 772 is used in conjunction with the sealing assembly. The container needle 772 is shown in a storage state, wherein the container needle 772 is positioned through a barrier 726 such that the needle tip 774 of the needle 772 is positioned in a space 760. In a delivery state (not shown), the needle tip 774 will pierce a flexible wall 724 and extend into a reservoir 740.

[0053] Compared with the previously discussed embodiments, Figure 10 The container 720 shown includes at least one bypass or vent 780. The bypass 780 is in fluid communication with the reservoir 740. The bypass 780 is selectively actuated to allow gas trapped between the barrier 726 and the flexible wall 724 to escape through the bypass 780 into the reservoir 740 as the sealing assembly moves between the shown storage and delivery states, wherein the barrier 726 advances in the direction of the flexible wall 724 to allow the needle 774 of the container needle 772 to penetrate the wall 724.

[0054] Bypass 780 is not in fluid communication with space 760 until the flexible wall 724 has been removed. Figure 10 The storage state shown has been moved to Figure 11 This concludes the intermediate state shown. Figure 10 and Figure 11 As shown, the bypass 780 can be defined in the inner surface 738 of the wall 722 and can take the form of a groove 782 formed in the wall 722. The groove 782 can have a distal end 784 and a proximal end 786. As will be appreciated, the reservoir 740 is sealed relative to the space 760 until the outer surface 730 of the flexible wall 724 moves past the distal end 784 of the groove 782. However, once the outer surface 730 of the flexible wall 724 moves past the distal end 784 of the groove 782, the gas trapped between the barrier 726 and the flexible wall 724 can be discharged into the reservoir 740. This can facilitate the movement of the barrier 726 and the needle 770 toward the flexible wall 724.

[0055] Other embodiments of this disclosure include those in which the container needle is not positioned to pass through the sealing assembly or in which the container needle is positioned to pass completely through the sealing assembly. Two such alternative examples are illustrated in Figure 12 and Figure 13 middle.

[0056] Figure 12 and Figure 13 An embodiment is shown in which the reservoir needle is positioned through a flexible wall (defining a stop or septum) and a valve is used to isolate the reservoir from the injection needle. The valve can also be used to control the outflow of medical fluids or pharmaceutical products from the reservoir within the container. In this way, the valve can be used to meter the amount of medical fluid or pharmaceutical product from the reservoir, or to delay the flow of the medical fluid or pharmaceutical product until, for example, a certain time delay has elapsed relative to receiving input from an input device (e.g., a button or switch).

[0057] Figure 12 A syringe 850 is shown, comprising a container 852, a fluid delivery system 854, and an actuator 856. The container 852 includes a flexible wall 860, which may be in the form of a septum. The flexible wall 860 has an inner surface 862 and an outer surface 864. The fluid delivery system 854 includes a container needle 866, an injection needle 868, and a flexible cannula or tube 870 connecting the container needle 866 and the injection needle 868. The injection needle 868 may be housed within a cap 872 that maintains the sterility of the needle 868.

[0058] A container needle 866 (and more specifically, the needle tip 874 of container needle 866) is positioned to pass through a flexible wall 860 and an inner surface 862. Needle 866 is thus in fluid communication with a sterile reservoir 880 and a medical fluid or pharmaceutical product 890 disposed within the reservoir 880. Fluid communication between container needle 866 and injection needle 868 is interrupted by a valve 900 disposed in or along a flexible tubing 870. (See above regarding...) Figures 1 to 11 Unlike the other embodiments discussed, the actuator 856 of the syringe 850 is not used to move the container needle 866 relative to the flexible wall 860, but instead operates the valve between a closed state in which fluid communication between the needles 866 and 868 is interrupted and an open state in which fluid communication between the container needle 866 and the injection needle 868 is established.

[0059] Valve 900 can take various shapes and forms, two of which are shown in Figure 12 and Figure 13 In China. To be clear, Figure 12An embodiment of syringe 850 is shown, wherein a rotatable valve 900 is disposed in a flexible tube 870 or has an internal valve component that is in fluid communication with a fluid flow path defined between a container needle 866 and an injection needle 868. Figure 13 An embodiment of the syringe is shown, wherein a clamp valve 902 is disposed along a flexible tube 870 and thus cooperates with the outer surface of the tube 870 to interrupt fluid communication between the container needle 866 and the injection needle 868.

[0060] For example Figure 12 and Figure 13 Embodiments of those shown can also be used for containers with permanently attached needles, such that the container is in the form of, for example, a syringe. Additionally, regarding... Figure 4 The described method can be used in any of the previously mentioned embodiments as well as for applications like... Figure 12 and Figure 13 In some of the embodiments shown, valves are not used, but the syringe (i.e., the container with a permanently attached needle) has a needle covered by a shield to maintain its sterility.

[0061] Figure 12 and Figure 13 The embodiments shown can be further modified to incorporate sealing assemblies comprising multiple walls and / or seals, such as (for example) Figure 7 As shown in the image. Figure 14 Such embodiments are shown.

[0062] To be clear, Figure 14 A syringe 920 is shown, comprising a container 922, a fluid delivery system 924, an actuator 926, and a sealing assembly 928. The fluid delivery system 924 may include a container needle 930, an injection needle 932, and a flexible cannula or tubing 934 connecting the container needle 930 and the injection needle 932. The injection needle 932 may be housed within a cap 936 that maintains the sterility of the needle 932. The needle 932 may also be in selective fluid communication with a sterile reservoir 940 and a medical fluid or pharmaceutical product 942 disposed within the reservoir 940 via a valve 944 disposed in or along the flexible tubing 934. In this respect, the syringe 920 is... Figure 12 and Figure 13 The syringe embodiments shown are similar.

[0063] However, the sealing assembly 928 of the syringe 920 also has a flexible wall 950 and a barrier 952. The flexible wall 950 and the barrier 952 each have an inner surface and an outer surface, wherein the inner surface of the flexible wall 950 partially defines and closes the sterile reservoir 940. The barrier 952 is positioned outside the flexible wall 950 to define an enclosure space 954 between the flexible wall 950 and the barrier 952, in which the needle 956 of the container needle 930 can be placed.

[0064] Figure 14 The embodiments have two potential barriers: one in the form of a valve 944, and the second in the form of a needle 956 positioned within space 954. In some embodiments, valve 944 can be controlled to provide a delay in the injection of medical fluid or pharmaceutical product 942 after the container needle 930 has penetrated the flexible wall 950 into reservoir 940.

[0065] The apparatus according to this disclosure may have one or more advantages over conventional technology, and any one or more of these advantages may be present in said particular embodiment according to the features of this disclosure included in said particular embodiment. As an example, these embodiments maintain the sterility of medical fluids or pharmaceutical products until the time of use. As another example, the possibility of mixing of medical fluids or pharmaceutical products is limited or eliminated before the time of use. As yet another example, unintentional delivery of medical fluids or pharmaceutical products is limited or prevented before the time of use.

[0066] For illustrative purposes only, Figure 15 Another method 1000 is provided for assembling a delivery device according to any of the embodiments disclosed above. Method 1000 follows the above description regarding... Figure 4 The general processing procedure is briefly described. However, it refers to the cleanroom classification according to GMP EU standards, rather than the cleanroom classification according to US Federal Standard 209E. Furthermore, Method 1000 provides additional optional paths (indicated as left or right branches) that can be followed during the assembly of the delivery device. Therefore, Figure 15 Method 1000 can be considered as the above regarding Figure 4 This is a supplement to the existing discussion.

[0067] Method 1000 for assembling the delivery device begins at frame 1002. The containers used in the device are initially stored in sealed boxes. These containers may be sterilized. At frame 1002, the boxes are unpacked (e.g., in a Class C cleanroom) using an automated unpacking machine. At frame 1004, within an isolator, for example in a space operating as a Class A cleanroom, or perhaps in a space otherwise operating as a Class C cleanroom, the Tyvek seal is peeled off (e.g., by a robot) and removed.

[0068] At frame 1006, in an isolator within a space operating as a Class A cleanroom, or perhaps otherwise operating as a Class C cleanroom, the container is filled, and a stop and fluid system are attached, and then the container is re-inserted into the open box. From this perspective, two different alternative paths or branches are possible.

[0069] At frame 1008, the filled container can remain in the open box. At frame 1010, the box can be transported and moved by trolley to a storage space (e.g., a cold storage room).

[0070] If the route of boxes 1008 and 1010 is followed, then method 1000 can continue, wherein the box is conveyed at box 1012 for processing in the inspection chamber. The filled containers are then unstacked from the open box at box 1014, and supplied to the automated inspection machine at box 1016. Automated inspection of the filled containers occurs at box 1016, followed by optional additional semi-automated or manual inspection at box 1018.

[0071] Alternatively, the box can be resealed, repackaged, and relabeled at frame 1020. For example, at frame 1020, the box can be resealed, repackaged, and then relabeled using Tyvek (e.g., using a Bausch + Strobel box sealer) in a Class C cleanroom. If necessary, the box can then be stored or even shipped at frames 1022 and 1024.

[0072] Once storage or transport is complete, the boxes are unpacked at frame 1026 (for example) using an automated unpacking machine. At frame 1028, the Tyvek seals are peeled off and removed. At frame 1030, the filled containers can then be unpacked for inspection. The actions at frames 1026, 1028, and 1030 are performed in a Class C cleanroom. At frame 1032, automated inspection can then be performed using a vision inspection machine designed to operate in a Class C cleanroom.

[0073] If either procedure is followed, at box 1034, the filled and inspected container can then be transferred to the rotary tray.

[0074] According to the first procedure, at box 1036, the rotary tray can be directly delivered to the storage area. If the route of box 1036 is followed, the rotary tray is then conveyed at box 1038 for processing in the device assembly chamber. At box 1040, the container is unstuffed, and at box 1042, it is assembled with other components of the delivery device to define the assembled delivery device (e.g., a syringe or infusion set).

[0075] Alternatively, the container can be moved into a box, which is then sealed, packaged, and labeled at frame 1044. For example, the box can be resealed, packaged, and labeled using Tyvek in a Class C cleanroom. If necessary, the box can then be stored or even shipped for further processing at frames 1046 and 1048. Once storage or shipping is complete, the box is unpacked at frame 1050 (e.g., using an automated unpacking machine). At frame 1052, the Tyvek seal is peeled off and removed, and the container is unpacked. At frame 1054, the filled container can then be assembled with the other components of the delivery device. The actions at frames 1050, 1052, and 1054 can all occur within a Class C cleanroom.

[0076] In either case, the assembled device is packaged at frame 1056, and the packaged assembled device is stored at frame 1058. Finally, at frame 1060, the packaged assembled device is delivered to the distributor and / or used for other distribution activities.

[0077] While numerous embodiments of the syringe have been described above, other embodiments are possible. Figures 16 to 22 and Figure 24 Numerous embodiments are shown that utilize mechanical connections or couplings between the container and the container needle. See also... Figures 16 to 18 According to such an additional embodiment, the syringe 1100 includes a container 1102, a sealing assembly 1104, and a fluid delivery system 1106, which includes a sterile container needle 1108. As discussed above, the fluid delivery system 1106 may include a sterile flexible tube connected at a first end to the container needle 1108 and at a second end to a sterile injection needle, the sterile injection needle being housed within a sterile cap that seals the sterile injection needle. Unlike the embodiments described above, the sterile container needle 1108 is attached to a connector 1110, which mechanically connects to or couples to the container 1102 to secure the sterile connector needle 1108 to the container 1102.

[0078] like Figure 16 As shown, container 1102 may have container wall 1120 having an inner surface 1122. In some embodiments, container 1102 may include a rigid wall formed using, for example, any material discussed above with respect to other containers discussed herein. Container 1102, and more specifically, container wall 1120, defines a borehole 1124, and container 1102 may include a stop (or plunger) 1126 movable along borehole 1124 between opposing ends 1128, 1130.

[0079] Although the plunger 1126 closes one end 1130 of the container 1102, the other end 1128 of the container 1102 is closed by a sealing assembly 1104. As shown, the sealing assembly 1104 includes a flexible sealing assembly wall 1140 and a barrier 1142.

[0080] The flexible sealing assembly wall 1140 has an inner surface 1144. The inner surfaces 1122 and 1144 of the container wall 1120 and the sealing assembly wall 1140 define a closed, sterile reservoir 1146 that can be filled with medical fluids or pharmaceutical products. The container 1102 has an opening 1148 at a first end 1128 of a bore 1124, the opening 1148 being in fluid communication with the reservoir 1146, and the flexible sealing assembly wall 1140 defines a septum disposed across the opening 1148. As described in detail below with respect to exemplary embodiments, the flexible sealing assembly wall 1140 is fixedly attached to the container wall 1120.

[0081] Barrier 1142 is disposed outside the sealing assembly wall 1140 (relative to reservoir 1146) to define an enclosing space 1150 between the flexible wall 1140 and barrier 1142. Specifically, barrier 1142 may have a cup-shaped shape defined by a plate 1152 having an outer surface 1154 and an inner surface 1156 and an edge 1158 extending axially from the inner surface 1156 of plate 1152. Surface 1160 of edge 1158 is disposed on outer surface 1162 of sealing assembly wall 1140, and enclosing space 1150 is disposed between inner surface 1156 of plate 1152, outer surface 1162 of sealing assembly wall 1140, and edge 1158. In some embodiments, barrier 1142 and flexible sealing assembly wall 1140 may be formed as a single structure defining the space therebetween.

[0082] Fluid delivery system 1100 includes a sterile container needle 1108. This needle 1108 has a needle tip 1170, which is in a stored state (see...). Figure 17 In the delivery state (see) it is arranged to pass only through barrier 1142 and in the delivery state (see) Figure 18 The sterile container needle 1108 is positioned to pass through the flexible wall 1140 into the sterile reservoir 1146. As mentioned above, the sterile container needle 1108 is attached to the connector 1110, which is mechanically attached to the container 1102 to secure the sterile container needle 1108 to the container 1102, wherein the needle 1108 is in a stored state. An actuator 1180 is included (see [link to actuator 1180]). Figure 16The actuator itself is adapted, for example, to move the container needle 1108 from a storage state to a delivery state after receiving a signal from a mechanical, electromechanical, or electrical input device coupled to the actuator 1180. According to some embodiments, the actuator 1180 is adapted to delay the movement of the container needle 1108 from the storage state to the delivery state to a predetermined time after receiving the input.

[0083] Various mechanisms can be used to mechanically connect or couple the connector 1110 to the container 1102. For example, the connector can be simply press-fitted into the container. Figure 19 An embodiment of the connector is shown, which is formed of a cup-shaped clamp 1190 through which the sterile container needle 1108 extends. The clamp 1190 has a plate 1192 having an outer surface 1194 and an inner surface 1196, and an edge 1198 extending axially from the inner surface 1196 of the plate 1192. The end of the container is received within a space 1200 defined by the inner surface 1196 of the plate 1192 and the edge 1198, and the inner surface 1202 of the edge 1198 frictionally engages the container to limit or prevent separation.

[0084] Alternatively, connector 1110 may be the first connector in a pair of connectors, and the second connector 1210 in the pair of connectors may be attached to container 1102. See (for example) Figures 16 to 18 The first and second connectors 1110 and 1210 can be mechanically coupled to, for example... Figure 17 In the storage state shown, the sterile container needle 1108 is secured to the container 1102. For example, a series of connectors available according to embodiments of this disclosure may include first and second connectors, each comprising one of a pair of opposing surfaces. The opposing surfaces abut to restrict axial movement of the first and second connectors along the longitudinal axis of the sterile container needle, and thus restrict or prevent separation of the sterile container needle from the container and sealing assembly.

[0085] Figures 16 to 18 and Figure 20 An embodiment of such a connector pair is illustrated. According to this embodiment, first and second connectors 1110, 1210 engage to rotatably couple the pair of connectors 1110, 1210 to secure the sterile container needle 1108 to the container 1102 in a storage state. That is, the illustrated first and second connectors 1110, 1210 restrict or prevent the sterile connector needle 1108 from separating from the container 1102 in the axial direction, but do not restrict or prevent the needle 1108 and the associated connector 1110 from rotating relative to the container / sealing assembly 1102 / 1104.

[0086] like Figure 20As seen, the connector includes a cup-shaped clamp 1220 through which a sterile container needle 1108 cantilevered. The clamp 1220 has a plate 1222 having an outer surface 1224 and an inner surface 1226, and an edge 1228 extending axially from the inner surface 1126 of the plate 1222. The edge 1228 defines an opening 1230 through which the end of the container 1102 is positioned when the sterile container needle 1108 is fastened to the container 1102. An inwardly pointing flange 1232 and an outwardly pointing flange 1236 are disposed around the opening 1230, the inwardly pointing flange defining one of a pair of opposing surfaces 1234, and the outwardly pointing flange, attached to the container 1102, defining the other surface 1238. See also Figure 16 and Figure 17 Once pin 1108 and connector 1110 have advanced in the direction of container 1102, the adjacency of opposing surfaces 1234, 1238 restricts or prevents separation, causing flange 1232 to move axially through flange 1236 in the direction of container 1102.

[0087] according to Figure 16 , Figure 17 and Figure 19 In the illustrated embodiment, container 1102 includes an edge 1240 disposed around an opening 1148. A sealing assembly 1104 is disposed over the opening 1148 of container 1102, wherein a portion of the sealing assembly wall 1140 is disposed through the opening 1148. A second connector 1210 includes an outwardly pointing flange 1246 defining an edge, at least a portion of the second connector 1210 defined by the edge 1246 being disposed over the sealing assembly 1104. Container 1102 further includes a crimping ring 1250 formed around the edge 1240 of container 1102 and the edge 1246 of the second connector 1210, wherein the sealing assembly 1104 is disposed between the edges 1240 and 1246 to secure the sealing assembly 1104 between the edge 1240 of container 1102 and the edge 1246 of the second connector 1210.

[0088] According to this embodiment, the second connector 1210 also has a passage 1252 through which it passes. The sterile container needle 1108 is positioned in a storage state to pass through the passage 1252 in the second connector 1210 and through the barrier 1142, and in a delivery state to pass through the passage 1252, the barrier 1142, and the sealing assembly wall 1140. Of course, such embodiments are included for illustrative purposes and not for limitation.

[0089] In order to assemble Figures 16 to 18The device shown allows the container needle 1108 and connector 1110 to advance in the direction of container 1102. As the needle 1108 passes through barrier 1142, the inward-pointing flange 1232 of connector 1110 moves past the outward-pointing flange 1236 of connector 1210 attached to container 1102. Once flange 1232 has moved past flange 1236, movement of container needle 1108 and associated connector 1110 is prevented by adjacent surfaces 1234, 1238. The materials selected for flanges 1232 and / or flange 1236 can be chosen to resist significant forces applied to container needle 1108 and connector 1110 to separate needle 1108 from container 1102. However, the material is also selected to allow flanges 1232, 1236 to move through each other, such that mechanical coupling can be formed, and / or the coupling 1220 of connector 1110 may have features (e.g., axial slots) that allow coupling 1220 or sections of coupling 1220 to flex to allow flange 1232 to move through flange 1236.

[0090] Figure 21 Connectors of different embodiments that can be used for connector pairs are shown. According to this embodiment, the first and second connectors in the connector pair are threadedly engaged to couple the connector pair to secure a sterile container needle to a container in a storage state. Therefore, relative rotational movement between the first and second connectors will cause the connectors to be securely coupled or decoupled from each other, and thus will limit relative rotational movement (with...). Figures 16 to 18 and Figure 20 The embodiments differ from those in which relative rotational motion is permitted. For example... Figure 21 As shown, the first connector in such a connector pair may have a clamp 1260 having a plate 1262 having an outer surface 1264 and an inner surface 1266, and an edge 1268 extending axially from the inner surface 1266 of the plate 1262. The edge 1268 defines an opening 1270 through which the end of the container is positioned when the sterile container needle is fastened to the container. A thread 1272 is formed on the inner surface of the edge 1268, which will mate with a mating thread formed on the second connector.

[0091] like Figures 16 to 21 As shown, the first connector in the connector pair may include a clamp continuously arranged around the sterile connector pin. Or, as... Figure 22 As shown, the first connector may include a clamp discontinuously arranged around the sterile connector pin. According to... Figure 22In the embodiment shown, the connector includes a clamp 1280 that is distinctly discontinuous, defining only to the extent that the clamp 1280 defines a pair of arms 1282 positioned opposite each other relative to a container pin 1108, which is positioned between the two arms 1282. The arms 1282 are connected to a plate 1284 having an outer surface 1286 and an inner surface 1288. Due to the relatively limited width of the arms 1282, the arms 1282 may have an end 1290 that attaches to the plate 1284 and defines a live hinge, thereby allowing the arms 1282 to pivot relative to the plate 1284 and the end 1290. The arms 1282 may also have inwardly pointing flanges or fingers 1292 that will correspond to the corresponding structure of the container (e.g., Figure 16 and Figure 17 The flange 1236 of the container 1102 shown engages to restrict or prevent axial movement between the container 1102 and the needle 1108, so that the container needle 1108 will separate from the container 1102.

[0092] Therefore, in Figure 23 The image shows the assembly of a syringe (e.g.) Figures 16 to 18 and Figure 19 Method 1300 of syringe 1100 shown. Method 1300 may include sterilizing reservoir 1146 at frame 1302 and filling the sterile reservoir 1146 of container 1102 with medical fluid or pharmaceutical product under aseptic conditions at frame 1304, reservoir 1146 being defined by the inner surface 1122 of the wall 1120 of container 1102. A sterile fluid delivery system 1106 (e.g., container needle 1108) may be mechanically connected or coupled to container 1102 under aseptic conditions, the fluid delivery system 1106 being not in fluid communication with reservoir 1146 in the storage state but in fluid communication with reservoir 1146 in the delivery state, and assembling the remaining portion of syringe 1100 under cleanroom conditions. Specifically, the steps of sterilizing and filling the sterile reservoir 1146 can follow the step of mechanically connecting or coupling the sterile fluid delivery system 1106 to the container 1102 (as shown in box 1306). According to other embodiments, the step of mechanically connecting or coupling the sterile fluid delivery system 1106 to the container 1102 (as shown in box 1308) can follow the step of filling the sterile reservoir 1146. The step of mechanically connecting or coupling the sterile fluid delivery system 1106 can occur, for example, within the filling / completion kit. Assembly of the remaining portion of the syringe 1100 can also include attaching the fluid delivery system 1106 to the actuator 1180 under cleanroom conditions at box 1310, the actuator 1180 being adapted to change the state of the fluid delivery system 1106 from a stored state to a delivery state.

[0093] The needle-to-container connection (and specifically to the flexible sealing assembly wall / barrier) prior to container sterilization and filling is not limited to... Figures 16 to 22 Implementation examples. It will be appreciated that, according to... Figure 23 The methods described in [the document] perform [actions] regarding [the specific tasks]. Figure 15 The described method is 1000. To be clear, it is not in... Figure 15 In method 1000, the container needle is assembled with the reservoir at box 1006. Alternatively, the container needle (and associated fitting / delivery needle) can be assembled with the reservoir even before box 1002, allowing the container needle / container assembly to be filled and re-nested in the box at box 1006. Method 1000 can then continue as described above.

[0094] It will also be recognized that, although systems in which a combination of sealing walls and barriers has been described, Figures 16 to 22 The embodiments, but can be utilized Figures 1 to 14 The embodiments described herein are intended to provide a similar system having a mechanical connection or coupling between a container needle and a container. To illustrate this, in Figure 24 Additional embodiments according to this disclosure are provided, wherein the syringe 1330 includes a container 1332, a sealing assembly 1334, and a fluid delivery system 1336 including a sterile container needle 1338. As discussed above, the fluid delivery system 1336 may include a sterile flexible tube connected at a first end to the container needle 1338 and at a second end to a sterile injection needle, the sterile injection needle being housed within a sterile cap that seals the sterile injection needle. The sterile container needle 1338 is attached to a connector 1340, which mechanically connects to or couples to the container 1332 to secure the sterile connector needle 1338 to the container 1332.

[0095] Container 1332 may have a container wall 1342 having an inner surface 1344 and a stop (or plunger) 1346 movable between opposing ends 1348, 1350. While the plunger 1346 closes one end 1350 of container 1332, the other end 1348 of container 1332 is closed by a sealing assembly 1334. As shown, the sealing assembly 1334 includes a flexible sealing assembly wall 1352.

[0096] The flexible sealing assembly wall 1352 has an inner surface 1354, and the inner surfaces 1344 and 1354 of the container wall 1342 and the sealing assembly wall 1352 define a closed sterile reservoir 1356. The container 1332 has an opening 1358 at a first end 1348 in fluid communication with the reservoir 1356, and the flexible sealing assembly wall 1352 defines a septum disposed across the opening 1358. The needle 1338 has a needle tip 1360, which, in the stored state, is positioned to partially penetrate the wall 1352 (e.g., ...). Figure 24 (as shown in the diagram) and in the delivery state, it is positioned to pass through the flexible wall 1352 into the sterile reservoir 1356.

[0097] As mentioned above, a sterile container needle 1338 is attached to a connector 1340, which is mechanically attached to a container 1332 to secure the sterile container needle 1338 to the container 1332, wherein the needle 1338 is in a stored state. Specifically, a second connector 1362 is connected to the container 1332. The connector 1340 has an inwardly pointing flange 1364 defining one of a pair of opposing surfaces 1366 and an outwardly pointing flange 1368 attached to the container 1332 and defining the other surface 1370. Once the needle 1338 and the connector 1340 have advanced in the direction of the container 1332, the abutment of the opposing surfaces 1366, 1370 restricts or prevents separation, such that the flange 1364 moves axially through the flange 1368 in the direction of the container 1332. Advantages and embodiments not explicitly listed herein may also be appreciated. For example, although the operation of the actuator has been described with respect to the foregoing embodiments as moving the container needle from a storage state to a delivery state, it will be understood that the actuator can also move the container needle from a delivery state to a storage state. If a dose of medical fluid or pharmaceutical product less than the volume of the reservoir is to be delivered (e.g., where the syringe is designed to deliver an adjustable dose according to the patient's needs (e.g., pediatric to adult patient), then the actuator can move the container needle from the storage state to the delivery state before the delivery of the dose and from the delivery state to the storage state after the delivery of the dose. The movement from the delivery state to the storage state effectively reseals the container and closes the fluid path to the patient. This sequence of movements between the storage state and the delivery state can be repeated. As noted above, it is advantageous to maintain a closed fluid path until the start of delivery because this reduces the chance of unintentionally delivering the medical fluid or pharmaceutical product to the patient and / or mixing the medical fluid or pharmaceutical product with the patient's bodily fluids.

[0098] The syringe according to this disclosure can be used in a variety of medical fluids or pharmaceutical products containing colony-stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF formulations include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pefilgrastim). In various other embodiments, the drug delivery device can be used in a variety of pharmaceutical products, such as erythropoiesis stimulants (ESAs), which can be in liquid or lyophilized form. ESA is any molecule that stimulates erythrocyte production, such as Epogen® (epogenetin α), Aranesp® (dabepoetin α), Dynepo® (epogenetin δ), Mircera® (methoxylated polyethylene glycol epogenetin β), Hematide®, MRK-2578, INS-22, Retacrit® (epogenetin ζ), Neorecormon® (epogenetin β), Silapo® (epogenetin ζ), Binocrit® (epogenetin α), epogenetin α Hexal, Abseamed® (epogenetin α), Ratioepo® (epogenetin θ), Eporatio® (epogenetin θ), Biopoin® (eporine θ), eporine α, eporine β, eporine ζ, eporine θ, and eporine δ, and molecules or variations thereof or analogues disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689; and PCT Publication Nos. WO 91 / 05867; WO 95 / 05465; WO96 / 40772; WO 00 / 24893; WO 01 / 81405; and WO2007 / 136752.

[0099] ESA can be an erythropoietin-stimulating protein. As used herein, "erythropoietin-stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor (e.g., by binding to the receptor and causing receptor dimerization). ESA includes erythropoietin and its variants, analogs, or derivatives 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. ESA includes, but is not limited to, epoetin α, epoetin β, epoetin δ, epoetin ω, epoetin ι, epoetin ζ and their analogs, pegylated erythropoietin, carbamylated erythropoietin, mimic peptides (including EMP1 / hematide) and mimic antibodies. Exemplary erythropoietin-stimulating proteins include erythropoietin, dabepoetine, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (and include compounds reported in U.S. Publications 2003 / 0215444 and 2006 / 0040858, the disclosure of each of which is incorporated herein by reference in its entirety), as well as erythropoietin molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety. The following methods are incorporated herein by reference: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086; 6,310,078; 6,391,633; 6,583,272; 6,586, 398; 6,900,292; 6,750,369; 7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002 / 0155998; 2003 / 0077753; 2003 / 0082749; 2003 / 0143202; 2004 / 0009902; 2004 / 0071694; 2004 / 0091961; 2004 / 0143857; 2004 / 0157293; 20 04 / 0175379; 2004 / 0175824; 2004 / 0229318; 2004 / 0248815; 2004 / 0266690; 2005 / 0019914; 2005 / 0026834; 2005 / 0096461; 2005 / 0107297; 2005 / 0107591; 2005 / 0124045; 2005 / 0124564; 2005 / 0137329; 2005 / 0142642;2005 / 0143292; 2005 / 0153879; 2005 / 0158822; 2005 / 0158832; 2005 / 0170457; 2005 / 0181359; 2005 / 0181482; 2005 / 0192211; 2005 / 0202538; 2005 / 0227289; 2005 / 0244409; 2006 / 0088906; and 2006 / 0111279; as well as PCT Publication Nos. WO 91 / 05867; WO 95 / 05465; WO 99 / 66054; WO 00 / 24893; WO 01 / 81405; WO 00 / 61637; WO 01 / 36489; WO 02 / 014356; WO 02 / 19963; WO 02 / 20034; WO 02 / 49673; WO 02 / 085940; WO 03 / 029291; WO 2003 / 055526; WO 2003 / 084477; WO 2003 / 094858; WO 2004 / 002417; WO 2004 / 002424; WO 2004 / 009627; WO 2004 / 024761; WO 2004 / 033651; WO 2004 / 035603; WO 2004 / 043382; WO 2004 / 101600; WO 2004 / 101606; WO 2004 / 101611; WO 2004 / 106373; WO 2004 / 018667; WO 2005 / 001025; WO 2005 / 001136; WO 2005 / 021579; WO 2005 / 025606; WO 2005 / 032460; WO 2005 / 051327; WO 2005 / 063808; WO 2005 / 063809; WO 2005 / 070451; WO 2005 / 081687; WO 2005 / 084711; WO 2005 / 103076; WO 2005 / 100403; WO 2005 / 092369; WO 2006 / 50959; WO 2006 / 02646; and WO 2006 / 29094.;

[0100] Examples of other pharmaceutical products that can be used with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (dinosema), and Prolia™ (dinosema); other biologics such as Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Neulasta® (pefilgrastim, pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), and Nplate® (romilastine); and small molecule drugs such as Sensipar® (cinacacet). The device may also be used with therapeutic antibodies, peptides, proteins, or other chemicals such as iron, for example, ferrimoxol, dextran iron, ferrous gluconate, and ferrous sucrose. The pharmaceutical products may be in liquid form or reconstituted from lyophilized form.

[0101] Specific illustrative proteins are the specific proteins described below, including their fusions, fragments, analogs, variants, or derivatives: OPGL-specific antibodies, peptides, and related proteins and analogues (also referred to as RANKL-specific antibodies, peptides, and analogues), including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, including but not limited to the antibodies described in PCT Publication No. WO 03 / 002713, the entire contents of which regarding OPGL-specific antibodies and antibody-related proteins are incorporated herein, particularly those antibodies and antibody-related proteins having the sequences stated therein, particularly but not limited to those sequences represented therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including those having as stated therein Figure 2 The light chain described herein, SEQ ID NO: 2 and / or as stated therein Figure 4 The OPGL-specific antibodies of the heavy chain SEQ ID NO:4 described herein, each of which is individually and explicitly incorporated herein by reference in its entirety, as disclosed in the foregoing publication; Myostatin-binding proteins, peptides, and related proteins, and the like, including myostatin-specific peptides, particularly those described in U.S. Publication No. 2004 / 0181033 and PCT Publication No. WO 2004 / 058988, which are incorporated herein by reference in their entirety, particularly in the sections relating to myostatin-specific peptides, including, but not limited to, peptides of the mTN8-19 family, including those of SEQ ID NOS: 305-351, including TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 con2; peptides of the mL2 family of SEQ ID NOS: 357-383; peptides of the mL15 family of SEQ ID NOS: 384-409; peptides of the mL17 family of SEQ ID NOS: 410-438; peptides of the mL20 family of SEQ ID NOS: 439-446; ... peptides of the mL20 family of SEQ ID NOS: 357-383; peptides of the mL20 family of SEQ ID NOS: 384-409; peptides of the mL15 family of SEQ ID NOS: 384-409; peptides of the mL15 family of SEQ ID NOS: 384-384; peptides of the mL15 family of SEQ ID NOS: 384-384; peptides of the mL15 family of SEQ ID NOS: 384-384; peptides of the mL1 The mL21 family of NOS:447-452; the mL24 family of SEQ ID NOS:453-454; and those of SEQ ID NOS:615-631, each of which is individually and explicitly incorporated herein by reference in its entirety, as fully disclosed in the foregoing publication; IL-4 receptor-specific antibodies, peptides, and related proteins and analogues, particularly those that inhibit activity mediated by the binding of IL-4 and / or IL-13 to the receptor, including those described in PCT Publication No. WO 2005 / 047331 or PCT Application Nos. PCT / US2004 / 37242 and US Publication No. 2005 / 112694, are incorporated herein by reference in their entirety, particularly in the section relating to IL-4 receptor-specific antibodies, especially antibodies to those described therein, particularly but not limited to those specified therein: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1, each of which is individually and explicitly incorporated herein by reference in its entirety, as fully disclosed in the foregoing publication; Interleukin-1 receptor 1 (“IL1-R1”) specific antibodies, peptides and related proteins and the like, including but not limited to those described in U.S. Publication No. 2004 / 097712A1, which is incorporated herein by reference in its entirety in the section relating to IL1-R1 specific binding proteins, particularly monoclonal antibodies, especially those indicated therein: 15CA, 26F5, 27F2, 24E12 and 10H7, each of which is individually and explicitly incorporated herein by reference in its entirety as disclosed in the aforementioned U.S. Publication; Ang2-specific antibodies, peptides, and related proteins and analogues, including but not limited to those described in PCT Publication No. WO 03 / 057134 and US Publication No. 2003 / 0229023, each of which is incorporated herein by reference in its entirety, particularly in the portions relating to Ang2-specific antibodies and peptides and analogues, especially those sequences described therein and including but not limited to: L1(N); L1(N) WT; L1(N) 1K WT; 2xL1(N); 2xL1(N) WT; Con4(N), Con4(N) 1K WT, 2xCon4(N) 1K; L1C; L1C1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C1K; Con4-L1(N); Con4-L1C; TN-12-9(N); C17 (N); TN8-8(N); TN8-14(N); Con 1 (N), also includes anti-Ang 2 antibody and formulation, such as PCT publication number WO Those described in 2003 / 030833, the entire contents of the publication concerning the antibodies therein are incorporated herein by reference, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1; AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AblA1; AblF; AblK; AblP; and AblP, in various arrangements thereof as described therein, each of which is individually and explicitly incorporated herein by reference in its entirety, as fully disclosed in the foregoing publication. NGF-specific antibodies, peptides, and related proteins, and the like, expressly including, but not limited to, those described in U.S. Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, which are incorporated herein by reference in their entirety, particularly with respect to NGF-specific antibodies and related proteins, expressly including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 specified therein, each of which is individually and expressly incorporated herein by reference in its entirety, as fully disclosed in the aforementioned publications; CD22-specific antibodies, peptides, and related proteins, and the like, such as those described in U.S. Patent No. 5,789,554, the entire contents of which are incorporated herein by reference, particularly human CD22-specific antibodies, such as, but not limited to, humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly including, but not limited to, human CD22-specific IgG antibodies, such as dimers of human-mouse monoclonal hLL2γ chain disulfides bonded to the human-mouse monoclonal hLL2k chain, including, but not limited to, human CD22-specific fully humanized antibodies in, for example, epazolizumab, CAS Registry No. 501423-23-0; IGF-1 receptor-specific antibodies, peptides, and related proteins, and similar substances, such as those described in PCT Publication No. WO 06 / 069202, the entire contents of which are incorporated herein by reference, including but not limited to the IGF-1 receptor-specific antibodies L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, and L26H2. 6. L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52 and IGF-1R binding fragments and their derivatives, each of which is individually and explicitly incorporated herein by reference in its entirety, as fully disclosed in the aforementioned international publication; Non-limiting examples of anti-IGF-1R antibodies used in the methods and compositions of the present invention include each and all of the antibodies described in the following cases: (i) U.S. Publications 2006 / 0040358 (published February 23, 2006), 2005 / 0008642 (published January 13, 2005), and 2004 / 0228859 (published November 18, 2004), including but not limited to (for example) antibodies 1A (DSMZ accession DSM ACC 2586), 8 (DSMZ accession DSM ACC 2589), 23 (DSMZ accession DSM ACC 2588), and 18 as described therein; (ii) PCT publications WO 06 / 138729 (published on December 28, 2006) and WO 05 / 016970 (published on February 24, 2005) and Lu et al. 2004, J Biol. Chem. 279:2856-65, contain, but are not limited to, antibodies 2F8, A12 and IMC-A12 as described therein; (iii) PCT publication numbers WO 07 / 012614 (published on February 1, 2007), WO 07 / 000328 (published on January 4, 2007), WO 06 / 013472 (published on February 9, 2006), WO 05 / 058967 (published on June 30, 2005) and WO 03 / 059951 (published on July 24, 2003); (iv) U.S. Publication No. 2005 / 0084906 (published on April 21, 2005), which includes, but is not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM 607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3 and antibody 7H2HM as described therein; (v) US Publication Nos. 2005 / 0249728 (published November 10, 2005), 2005 / 0186203 (published August 25, 2005), 2004 / 0265307 (published December 30, 2004), and 2003 / 0235582 (published December 25, 2003), and Maloney et al. 2003, Cancer Res. 63:5073-83, including, but not limited to, the antibody EM164, the novel surface EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3 as described therein; (vi) U.S. Patent Nos. 7,037,498 (published May 2, 2006), 2005 / 0244408 (published November 30, 2005), and 2004 / 0086503 (published May 6, 2004), and Cohen et al., 2005, Clinical Cancer Res. 11:2063-73, for example, antibody CP-751,871, comprising, but not limited to, each antibody generated from a hybridoma having ATCC search numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793 as described therein, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3; (vii) US Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004) contain, but are not limited to, antibodies 19D12 as described therein, and antibodies including the heavy chain 15H12 / 19D12 HCA (γ4) encoded by polynucleotides in the plasmid (deposited at ATCC with accession number PTA-5214) and the light chain 15H12 / 19D12 LCF (κ) encoded by polynucleotides in the plasmid (deposited at ATCC with accession number PTA-5220); and (viii) U.S. Publication No. 2004 / 0202655 (published on October 14, 2004), which includes, but is not limited to, the antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5 as described therein; each or all of which are incorporated herein by reference in their entirety, and particularly with respect to the aforementioned antibodies, peptides, and related proteins and the like targeting the IGF-1 receptor; B-7-related protein 1 specific antibodies, peptides, related proteins, and analogues (“B7RP-1”, also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, especially fully human IgG2 monoclonal antibodies that bind to epitopes in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with its natural receptor ICOS (specifically on activated T cells), in all the foregoing respects, especially those disclosed in U.S. Publication No. 2008 / 0166352 and PCT Publication No. WO 07 / 011941, the entire contents of which are incorporated herein by reference, including but not limited to the antibodies specified therein, as follows: 16H (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:1 and SEQ ID NO:7, respectively); 5D (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:2 and SEQ ID NO:9, respectively); 2H (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:3 and SEQ ID NO:10 respectively); 43H (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14 respectively); 41H (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:5 and SEQ ID NO:13 respectively); and 15H (wherein having light chain variable and heavy chain variable sequences SEQ ID NO:4 and SEQ ID NO:12 respectively), each of which is individually and explicitly incorporated herein by reference in its entirety as disclosed in the aforementioned U.S. publication; IL-15 specific antibodies, peptides, and related proteins, and the like, specifically, humanized monoclonal antibodies, particularly those disclosed in U.S. Publication Nos. 2003 / 0138421, 2003 / 023586, and 2004 / 0071702 and U.S. Patent No. 7,153,507, the entire contents of each of these claims relating to IL-15 specific antibodies and related proteins are incorporated herein by reference, including peptides, particularly including, but not limited to, HuMax IL-15 antibodies and related proteins, such as 146B7; IFNγ-specific antibodies, peptides, and related proteins and similar substances, especially human IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as those described in U.S. Publication No. 2005 / 0004353, the entire contents of which are incorporated herein by reference, particularly antibodies 1118, 1118*, 1119, 1121, and 1121* as specified therein. The complete sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their variable and complementary regions, are individually and explicitly incorporated herein by reference in their entirety, exactly as disclosed in the aforementioned U.S. Publication and Thakur et al., Mol. Immunol. 36:1107-1115 (1999). Furthermore, the descriptions of the properties of these antibodies provided in the aforementioned U.S. Publication are also incorporated herein by reference in their entirety. The specific antibodies include those having the heavy chain SEQ ID NO: 17 and the light chain SEQ ID NO: 18; those having the heavy chain variable region SEQ ID NO: 6 and the light chain variable region SEQ ID NO: 8; those having the heavy chain SEQ ID NO: 19 and the light chain SEQ ID NO: 20; those having the heavy chain variable region SEQ ID NO: 10 and the light chain variable region SEQ ID NO: 12; those having the heavy chain SEQ ID NO: 32 and the light chain SEQ ID NO: 20; those having the heavy chain variable region SEQ ID NO: 30 and the light chain variable region SEQ ID NO: 12; those having the heavy chain sequence SEQ ID NO: 21 and the light chain sequence SEQ ID NO: 22; those having the heavy chain variable region SEQ ID NO: 14 and the light chain variable region SEQ ID NO: 16; those having the heavy chain SEQ ID NO: 21 and the light chain SEQ ID NO: 33; and those having the heavy chain variable region SEQ ID NO: 14 and the light chain variable region SEQ ID NO: 31, as disclosed in the aforementioned U.S. publication. The expected specific antibody is antibody 1119, which is disclosed in the aforementioned U.S. publication and has the complete heavy chain SEQ ID NO:17 as disclosed therein and the complete light chain SEQ ID NO:18 as disclosed therein; TALL-1 specific antibodies, peptides and related proteins and analogues, as well as other TALL-1 specific binding proteins, such as those described in U.S. Publications 2003 / 0195156 and 2006 / 0135431, the entire contents of each of the publications relating to TALL-1 binding proteins (particularly the molecules in Tables 4 and 5B) are incorporated herein by reference, each of which is individually and explicitly incorporated herein by reference in its entirety, as disclosed in the aforementioned U.S. publications; Parathyroid hormone (“PTH”) specific antibodies, peptides and related proteins and the like, such as those described in U.S. Patent No. 6,756,480, which is incorporated herein by reference in its entirety, particularly in the section relating to proteins that bind to PTH. Thrombopoietin receptor (“TPO-R”) specific antibodies, peptides and related proteins, and the like, such as those described in U.S. Patent No. 6,835,809, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind to TPO-R; Hepatocyte growth factor (“HGF”) specific antibodies, peptides, and related proteins and the like, including those targeting the HGF / SF:cMet axis (HGF / SF:c-Met), such as the fully human monoclonal antibody that neutralizes hepatocyte growth factor / scattering factor (HGF / SF) as described in U.S. Publication No. 2005 / 0118643 and PCT Publication No. WO2005 / 017107, huL2G7 as described in U.S. Patent No. 7,220,410, and OA-5d5 as described in U.S. Patent Nos. 5,686,292 and 6,468,529, and PCT Publication No. WO 96 / 38557, each of which is incorporated herein by reference in its entirety, particularly in the section relating to proteins that bind HGF; TRAIL-R2 specific antibodies, peptides, related proteins and the like, such as those described in U.S. Patent No. 7,521,048, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind to TRAIL-R2; Activin A-specific antibodies, peptides, related proteins and the like, including but not limited to those described in U.S. Publication No. 2009 / 0234106, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind to activin A; TGF-β specific antibodies, peptides, related proteins, and the like, including but not limited to those described in U.S. Patent No. 6,803,453 and U.S. Publication No. 2007 / 0110747, each of which is incorporated herein by reference in its entirety, particularly in the section relating to proteins that bind TGF-β; β-amyloid-specific antibodies, peptides, related proteins, and the like, including but not limited to those described in PCT Publication No. WO2006 / 081171, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind β-amyloid. One anticipated antibody is the one disclosed in the aforementioned international publication, having a heavy chain variable region comprising SEQ ID NO: 8 and a light chain variable region comprising SEQ ID NO: 6; c-Kit specific antibodies, peptides, related proteins and the like, including but not limited to those described in Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind to c-Kit and / or other stem cell factor receptors; OX40L-specific antibodies, peptides, related proteins, and the like, including but not limited to those described in U.S. Application No. 11 / 086,289, which is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind to OX40L and / or other ligands of the OX40L receptor; and Other exemplary proteins include Activase® (alteplase, tPA); Aranesp® (dabepoetin α); Epogen® (epogenetin α or erythropoietin); GLP-1, Avonex® (interferon β-1a); Bexxar® (tosimomab, anti-CD22 monoclonal antibody); Betaseron® (interferon β); Camppath® (alemumab, anti-CD52 monoclonal antibody); Dynepo® (epogenetin δ); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex® (epogenetin α); Erbitux® (Cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (growth hormone, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu (erbB2) receptor mAb); Humatrope® (growth hormone, human growth hormone); Humira® (adalimumab); Insulin solution; Infergen® (compound interferon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (analysin); Leukine® (saxaglastine, rhuGM-CSF); LymphoCide® (epazolizumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (teneteleteplase, t-PA analog); Mircera® (Methoxylated polyethylene glycol-epotizine β); Mylotarg® (gem-tuzumab / olzomircin); Raptiva® (efalizumab); Cimzia® (cetuzumab, CDP 870); Soliris™ (eculizumab); Peroxyzumab (anti-C5 complement); Numax® (MEDI-524); Lucentis® (ranibuzumab); Panorex® (17-1A, ezolomide); Trabio® (lenodexumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43).13); Nuvion® (Vesizumab); Mecanzumab (huC242-DM1); NeoRecormon® (Epotetin β); Neumega® (Interleukin, Human Interferon-11); Neulasta® (Pegylated Filgrastim, Pegylated G-CSF, Pegylated hu-Met-G-CSF); Neupogen® (Filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3® (Moromab-CD3, Anti-CD3 Monoclonal Antibody); Procrit® (Epotetin α); Remicade® (Infliximab, Anti-TNFα Monoclonal Antibody); Reopro® (Abciximab, Anti-GP IIb / Ilia Receptor Monoclonal Antibody); Actemra® (Anti-IL6 Receptor mAb); Avastin® (Bevacizumab), HuMax-CD4 (Zamumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®- (α-interferon-2a); Simulect® (baliximab); Prexige® (lumiracoxib); Synagis® (palizumab); 146B7-CHO (anti-IL15 antibody, see US Patent No. 7,153,507); Tysabri® (natezumab, anti-α4 integrin mAb); Valortim® (MDX-1303, anti-B).Anthrax protective antigen mAb); ABthrax™; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 blockers (extracellular domains of the Fc region of human IgG1 and two IL-1 receptor components (type I receptor and receptor accessory protein); VEGF blockers (Ig domain of VEGFR1 fused to IgG1 Fc); Zenapax® (daktarizumab); Zenapax® (daktarizumab, anti-IL-2Rα mAb); Zevalin® (teimomab); Zetia® (ezetimibe); Orencia® (asceticipeptide, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (ruximab); BR2-Fc (huBR3 / huFc fusion protein (soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapamumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (orgrixumab, anti-CD20 human mAb); HuMax-EGFR (zarumulumab); M200 (voloximab, anti-α5β1 integrin mAb); MDX-010 (iplimab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C.Clostridium difficile toxin A and toxin BC mAbs MDX-066 (CDA-1 and MDX-1388); anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adenomyumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF Fibrogen (FG-3019) for stage I idiopathic pulmonary fibrosis; anti-CTLA4 mAb; anti-eosinophil chemokine 1 mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb; anti-ganglioside GM2 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-inflammatory); 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, CNTO 95); Anti-IP10 ulcerative colitis mAb (MDX-1100); Anti-LLY antibody; 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-TGFβ mAb (GC-1008); anti-TRAIL receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR / Flt-1 mAb; anti-ZP3 mAb (HuMax-ZP3); NVS antibody #1; and NVS antibody #2.

[0102] It may also contain sclerosing antibodies, such as, but not limited to, romosozumab, brosozumab, or BPS 804 (Novartis). It may also contain therapeutic antibodies, such as rilotumumab, bixalomer, trebananib, ganytumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab (denosumab), NPLATE, PROLIA, VECTIBIX, or XGEVA. Additionally, the device may contain a monoclonal antibody (IgG) binding to human proprotein convertase subtilisin / Kexin type 9 (PCSK9), such as US... 8,030,547, US13 / 469,032, WO2008 / 057457, WO2008 / 057458, WO2008 / 057459, WO2008 / 063382, WO2008 / 133647、WO2009 / 100297、WO2009 / 100318、WO2011 / 037791、WO2011 / 053759、WO2011 / 053783、WO2008 / 125 623, WO2011 / 072263, WO2009 / 055783, WO2012 / 0544438, WO2010 / 029513, WO2011 / 111007, WO2010 / 077854, WO2012 / 088313, WO2012 / 101251, WO2012 / 101252, WO2012 / 101253, WO2012 / 109530 and WO2001 / 031007.

[0103] It may also contain talimogene laherparepvec (T-Vec) or another oncolytic HSV for the treatment of melanoma or other malignancies. Examples of oncolytic HSVs include, but are not limited to, talimogene laherparepvec (T-Vec) (US 7,223,593 and US 7,537,924); OncoVEXGALV / CD (US 7,981,669); OrienX010 (Lei et al. 2013, World Journal of Gastroenterology, 19:5138-5143); G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. 2002, Cancer Gene Ther, 2002, 9 (12):967-978).

[0104] It also includes TIMP. TIMP is a tissue inhibitor of endogenous metalloproteinases (TIMP) and is important in many natural processes. TIMP-3 is expressed by various cells or present in the extracellular matrix; it inhibits all major cartilage degenerative metalloproteinases and can play a role in many degenerative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as in malignant tumors and cardiovascular diseases. The amino acid sequence of TIMP-3 and the nucleic acid sequence of the DNA encoding TIMP-3 are disclosed in U.S. Patent 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP gene mutations can be found in US 61 / 782,613, US 61 / 798,160, US 61 / 802,988, and US61 / 940,67.

[0105] It also includes antagonistic antibodies targeting the calcitonin gene-related peptide (CGRP) receptor and other headache targets, specifically for human CGRP receptor and bispecific antibody molecules. More information about these molecules can be found in WO2A075238A1.

[0106] Additionally, bispecific T-cell binder antibodies (BiTe), such as blinotumomab, can be used in the device. Alternatively, the device may contain an APJ macromolecular agonist, such as apralin or an analogue thereof. Information relating to such molecules can be found in PCT / 2013 / 075773, each of which (US and PCT) is incorporated herein by reference in its entirety, particularly in the sections relating to proteins that bind PCSK9.

Claims

1. A syringe, comprising: A container, the container comprising a container wall having an inner surface, wherein the container wall defines a drilled hole; A sealing assembly comprising a wall and a barrier, the wall being fixedly attached to a container wall and the barrier having a cup-shaped shape with an edge that contacts the outer surface of the wall of the sealing assembly to define an enclosure space between the wall of the sealing assembly and the barrier of the sealing assembly; A fluid delivery system comprising a container needle having a tip, the tip being positioned in a storage state such that the container needle is not in fluid communication with the borehole only through the barrier of the sealing assembly, and in a delivery state such that the container needle is in fluid communication with the borehole through the wall of the sealing assembly, wherein the barrier and the wall of the sealing assembly define the enclosed space in both the storage state and the delivery state; and A connector that couples the container needle to the container such that the tip of the container needle is positioned in the enclosed space in the storage state.

2. The syringe according to claim 1, wherein, The container wall at least partially defines the reservoir.

3. The syringe according to claim 2, wherein, The reservoir is filled with medical fluids or pharmaceutical products.

4. The syringe according to claim 3, wherein, The medical fluid or pharmaceutical product contains granulocyte colony-stimulating factor (G-CSF).

5. The syringe according to claim 4, wherein, The G-CSF is polyethylene glycol-modified.

6. The syringe according to claim 3, wherein, The medical liquid or pharmaceutical product contains: erythropoiesis stimulants; TNF blockers; interleukin receptor-specific antibodies; IGF receptor (insulin growth factor receptor)-specific antibodies; TGF-specific antibodies; or PCSK9 (proprotein convertase subtilisin / Kexin type 9)-specific antibodies.

7. The syringe according to claim 1, wherein, The connector is press-fitted into the container.

8. The syringe according to claim 1, wherein, The connector is a first connector in a pair of connectors, and a second connector in the pair of connectors is attached to the container. The first connector and the second connector are mechanically coupled to secure the container pins to the container in the storage state.

9. The syringe according to claim 8, wherein, The first connector and the second connector each include one of a pair of opposing surfaces that are adjacent to each other to restrict axial movement of the first connector and the second connector along the longitudinal axis of the container needle.

10. The syringe according to claim 9, wherein, The first connector and the second connector engage to rotatably couple the pair of connectors to secure the container pin to the container in the storage state.

11. The syringe according to claim 8, wherein, The first connector includes a coupling disposed continuously or discontinuously around the connector pin.

12. The syringe according to claim 1, wherein, The container wall defines an opening at the first end of the borehole, and the wall defines a partition that is disposed across the opening and fixedly attached to the container wall.

13. The syringe according to claim 1, wherein, The fluid delivery system includes a sterile flexible tube connected at a first end to the container needle and at a second end to the injection needle.

14. The syringe according to claim 1, wherein, The barrier and the wall are fixed relative to each other to define the enclosed space between them.

15. The syringe according to claim 1, wherein, The barrier and wall of the sealing assembly are formed as a single structure defining the enclosed space.

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