Device and method for vial transfer and injection

Abstract

To provide a disposable single-use device for transferring contents of one or more vials to a disposable injection device and mixing them.SOLUTION: A device for filtering a liquid drug comprises a housing including an injectable fluid passage, and a liquid drug filter with a liquid drug pore diameter or a liquid drug effective pore diameter, which is arranged within the injectable fluid passage and which is constituted to remove particulate matter.SELECTED DRAWING: Figure 17

Description

Technical Field

[0001] This application claims the benefit and priority of both U.S. Provisional Patent Application No. 61 / 979,816, filed on April 15, 2014, and U.S. Provisional Patent Application No. 61 / 836,266, filed on June 18, 2013, which are hereby incorporated by reference in their entirety.

[0002] The subject matter of the present application generally relates to devices and methods for administering the contents of vials, and more particularly to a disposable, single-use instrument and method for transferring and mixing the contents of one or more vials into a disposable injection device for administration to a human-like subject.

Background Art

[0003] Vials are one of the preferred container closure systems used by the pharmaceutical industry because of the wide variety of drugs and their extensive medical history and long-term stability records. Pharmaceuticals, including biologics, are often first introduced commercially in standard containers such as vials. Additionally, the industry has made significant investments in the major equipment for aseptic vial filling. However, vials require the transfer of the drug from the vial to an injection device for delivery to the patient. New sealed systems such as pre-filled syringes and cartridges have been introduced, which allow for the direct transfer of the drug from the syringe or cartridge to the patient. Injection devices such as auto-injectors and pens have been developed to take advantage of these newer forms of sealed containers. Due to the uncertainty of long-term drug stability and the already appropriate extensive manufacturing resources, devices that incorporate standard container closure systems such as vials, pre-filled syringes or cartridges are highly preferred in the pharmaceutical industry over devices that require a unique form of drug encapsulation.

[0004] However, vials, pre-filled syringes and cartridges are not necessarily the optimal containers for drug delivery devices. This is especially true for delivery devices that deliver relatively high volume drugs (2 - 20 cc) or high viscosity drugs (above 15 cP). Most vials, pre-filled syringes and cartridges are made of glass, which imposes design constraints in terms of strength and shape. Typical syringes and auto-injectors are limited not only by the forces applied to the glass sealed container system, but also by the viscosity of the drug that can be delivered. New injection devices that use unique sealed containers for insulin delivery have been developed, but these systems are very expensive, cannot generate high forces or pressures, and are generally not reusable and / or refillable.

[0005] Due to factors including stability and time to market, pharmaceuticals, including biologics, are often first marketed in lyophilized, or powdered, or concentrated liquid form. Drugs packaged in vials in such liquid or powder forms may require significant preparation prior to administration. To facilitate administration of liquid formulations in vials, vial drugs are often packaged with an empty syringe and multiple needles for aspiration from the vial and injection into the patient. In the case of powder formulations, an additional diluent or solution vial may be provided for reconstituting the powder formulation into a solution available for injection.

[0006] The risks associated with the preparation and administration of these dosage forms are significant. The risks include not only needle stick injuries during reconstitution and administration procedures, but also the potential for inappropriate mixing, inaccurate dosing, and incorrect concentrations. This is truly a labor-intensive task for both trained caregivers and patients receiving drug therapy. Similar risk issues can also apply to the transfer of pre-injection prepared drugs that must be transferred from vials to injection devices. This transfer requires the removal of the drug from the vial, measurement of the appropriate dose, and injection into the patient using a syringe. Incomplete transfer of the maximum volume of the vial requires overfilling the vial by 25-30% and the associated waste. Contamination of the injectable drug can occur due to non-sterile outside air being introduced into the vial or contamination of the drug by improper aseptic technique.

[0007] Accordingly, there continues to be a need for new and / or improved devices and methods for the transfer, mixing, and injection of drugs from a source vial or vials to a subject.

[0008] The following description is for illustrative purposes only and is not intended to be limiting. The subject matter may be applied to various devices, systems, and methods not described herein. SUMMARY OF THE INVENTION

[0009] The subject matter is, in one aspect, directed to a disposable, single-use device and method that, preferably by user initiation, automatically mixes and / or transfers the injectable contents of one or more vials into a single injection device and, preferably simultaneously, subsequently automatically applies pressure to the injection device to inject the patient. The contents of the vial can be any suitable injectable drug for the purposes of this description and the claims. "Injectable drug" includes, without limitation as to drug type, therapeutic, diagnostic, antibiotics, biologics, sedatives, sterile water, and other injectable materials, either alone or in combination with other injectable agents, regardless of the need for pre-injection reconstitution or concentration adjustment or other processes. Although various features of the subject matter may be described in the context of reconstitution for injection of powder formulations, the devices and methods disclosed herein are not limited to specific applications and can also be used for liquid injectable drugs that only require preparation for injection and transfer from the vial to the injection device. Further, the disclosed devices and methods may be used for injectable drugs that do not require reconstitution or concentration adjustment and are pre-mixed (such that two liquid agents are mixed for drug therapy) prior to injection or for injection applications.

[0010] The apparatus and method described herein can have any suitable detailed structure, but preferably is a structure for transferring the contents of a vial to an injection device. The apparatus can also be configured to mix or process the contents of a vial that require reconstitution or concentration adjustment during the transfer process. The apparatus can also be configured such that a user can select the dosage of the injection, and can further include a lockout feature that requires such a selection before the contents of the vial are allowed to communicate or be transferred by the device, or before mixing or other processing is initiated. The apparatus can further be configured to filter the drug before transferring it to the injection device to remove particulates and drug particles, and can include a sterile filter for filtering the replacement air that is vented to the vial or vials. The device can also include a lockout to prevent the user from removing or operating the injection device before the drug is transferred until the injection device is removed from the transfer apparatus.

[0011] The subject matter may include a vial holder configured to hold one or more vials in a predefined relationship for cooperation with a transfer device. For example, the vial holder may be configured to include one receiving area or cavity for one vial (e.g., a vial containing a liquid agent). Or, the vial holder may be configured to include a first vial receiving area or cavity for a first vial (such as a vial containing a lyophilized drug) and a second vial receiving area or cavity for a second vial (such as a vial containing a diluent). The vial holder includes vials in a predefined relationship so as to cooperate with the transfer device to carry or, if necessary, access and process the contents of the vials (e.g., mix and reconstitute the drug). The vial may be configured to only accept receiving a vial containing a diluent in one of the receiving areas and a powder vial in the other receiving area to prevent the vials from being confused at the wrong positions. The vial holder may include a removable cover configured to be attached onto the vial cap so as to cover the access member of the vial. Removal of the cover simultaneously removes the vial cap and exposes the vial to the access member for a prior aseptic application or connection to the transfer device if necessary. If the vial cap is kept sufficiently sterile by the cover, although preferable for taking sufficient care, the application may not be necessary. Alternatively, the vial holder with the vial inserted may be mounted on the transfer device with the vial cap removed. The sterility of the vial stopper and the vial access member is maintained throughout the life of the product, eliminating the need for the user to remove the vial cap and wipe the top of the vial.

[0012] The present subject matter includes any suitable detailed-structured injection device, and in particular, injection devices that are useful in combination with this instrument are all incorporated herein by reference: U.S. Patent Application No. 61 / 326,492 filed on April 21, 2010, U.S. Patent Application No. 13 / 637,756 filed on September 27, 2012, and U.S. Patent Application No. 61 / 704,922 filed on September 24, 2012. As seen in these applications, the illustrated injection device uses an expandable member like a balloon to automatically release or inject the drug when activated by the user. Long-term storage of the drug within a pressurized member poses difficulties in design and manufacture. A particularly advantageous aspect of one embodiment of the present subject matter is that the injection device can remain in a non-pressurized state (e.g., not filled, not inflated, in a low-energy state balloon), and the injectable drug remains in a standard original vial or multiple vials during an enhanced shelf life until injection is required. At this time, the injectable drug is preferably automatically transferred from the vial or multiple vials to the injection device (along with any associated mixing, dilution, or other required processing) by a transfer device, and the transfer device simultaneously charges the injection device (e.g., inflates the expandable member or balloon by introducing the injectable drug under pressure) so that the injection device is prepared for an automated injection to a patient as disclosed by the user. In this application, the injectable drug is in the injection device for only a very limited time, such as a few seconds or minutes, and the shelf life, design, and pharmaceutical materials for long-term drug storage are reduced.

[0013] According to another aspect of the present subject matter, which can be used with any suitable injection device, the expandable member (such as a balloon) may be configured to be extended and gradually collapse from one end to the other during injection. Although the specific structure may vary, generally, the arrangement of the extended expandable member, which is a flat coil or helical structure, allows a relatively small-sized expandable member with a significant length and volume expansion to be applied onto and left on the patient's skin. The injection device may have a viewing window for the user to visually recognize the expandable member and to check the general state of the injection based on the amount of the foldable and / or expandable part, and / or the expandable member or the viewing window may be marked with appropriate graduations to enable the user to determine the amount of the injection.

[0014] The vial holder, the transfer device, the injection device, and their methods of use are separate aspects of the present subject matter, each having its own utility and being separately claimed. However, they are configured and claimed in various combinations or partial combinations, such as the combination of the transfer device and the injection device, or the combination of the vial holder, the transfer device, and the injection device and / or methods of using such combinations.

Brief Description of the Drawings

[0015] Specific examples of the subject matter of the present application are shown by the accompanying drawings for illustrative purposes only and not for limitation.

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DETAILED DESCRIPTION OF THE INVENTION

[0016] As shown in FIGS. 1 and 2, and more particularly as described below, the disposable single - use single - vial transfer and injection system 1 shown in FIG. 1 may include a single vial holder 2, a transfer device 3, and an injection device 7. The disposable single - use two - vial mixing, transfer and injection system 4 shown in FIG. 2 may include a two - vial holder 5, a transfer device 6, and an injection device 7. As previously mentioned, each aspect has separate utility and may be claimed separately and / or in combination, or in sub - combinations.

[0017] As shown in FIGS. 3 and 4, the single vial holder 2 includes a housing 8 that includes a side wall 9, an end wall 10, and an opening or viewing window 11. Alternatively, the material of the vial holder 2 may be transparent in order to allow visualization of the contents of the vial 12. As shown in FIG. 4, the housing 8 is formed to define at least one or two or more cavities 13 or regions for vial accommodation to securely hold the vial 12 in each cavity 13. For example, the cavities 13 of the vial holder 5 may be sized to receive standard injectable vials 12 of different sizes from 1 to 30 ml. The vials 12 can be of the same size or different sizes and can contain any desired contents (fluids, liquids, injectable drugs, agents, or mixtures) 14. In the two - vial holder 5 illustrated in FIG. 4, the vials can include a vial 15 of powder, lyophilized, or liquid medicine, and a vial 16 of liquid or diluent. The vial holder 5 may have pre - packaged and assembled vials therein, for example, by a pharmaceutical manufacturer, or may have vials inserted into the vial holder 5 by an end - user or a medical professional such as a pharmacist or a nurse. The vial holder 5 may have appropriate patterns and / or features to allow only the assembly of a specific vial into a specific cavity 13. For example, the powder vial 15 may be inserted into a specific cavity 13 of the vial holder 5, and the diluent vial 16 may be inserted into another cavity 13 of the vial holder 5. The opening or viewing window 11 of the vial holder 5 allows direct visualization of the contents 14 of the vial.

[0018] As shown in FIGS. 3 and 4, as a further option, the vial holder 5 can be an assembly of individual vial holders 2, each having a single vial 12. For example, if necessary, the manufacturer of the injectable drug may pre-assemble the vial 12 in an independent vial holder 2 that can be coupled to the vial holder 2 of another vial 12 during injection if needed. For example, the pharmaceutical manufacturer may provide a lyophilized drug in a vial holder 2 and a diluent such as sterile water or saline in a separate vial holder. The user or medical professional can, if desired, couple the individual vial holders 2 to form a vial holder assembly (vial holder 5) for coupling to the transfer device 6 shown in FIG. 2.

[0019] Returning to FIG. 3, the vial holder 2 can typically include a removable cover 17 that covers and protects the end 18 of the vial during transportation and storage. A typical and standard commercial vial 12 includes a pierceable septum 19 located at the neck of the vial to access the contents 14 of the vial, which is covered by a removable vial cap (or closure) 20. Removal of the cover can simultaneously remove the vial cap 20 and expose the septum 19 of the vial to access the contents 14 after a sanitizing application of the septum 19 that the user may consider necessary. The removable cover 17 can be configured to engage the vial cap 20 such that removal of the vial cap 20 with the cover 17 may recess the vial 12 therein, and the pierceable septum 19 is fitted within the scope of the vial holder 2 as shown in FIG. 1 to reduce the chance of contamination by the user prior to insertion of the vial holder 2 into the transfer device 3. This system can be applied to a single vial holder 2 and a double vial holder 5.

[0020] As shown in FIG. 3, the vial holder 2 may include a connecting device 27 to prevent the vial 12 from being removed once it has been inserted into the vial holder 2. This helps to prevent the vial 12 from falling out or being accidentally removed during handling.

[0021] As shown in FIG. 5, the vial holder 5 may be assembled to the transfer device 6 with the vial cap removed and the vial inside the vial holder 5 by the device manufacturer. The exposed septum 19 of the vial is held adjacent to the vial access members 21, 52 prior to activation. This configuration provides convenience by eliminating the need for the user to remove the vial cap, wipe the septum at the top of the vial, and assemble the vial holder 5 to the transfer device 6 before using the system 4.

[0022] As shown in FIG. 6, the vial holder 2 may be packaged separately from the transfer device 3. In this case, the user removes the vial cap with the removable cover 17, wipes the septum 19 at the top of the vial (if necessary), and incorporates the vial holder 2 into the transfer device 3. As shown in FIG. 6, the vial holder 2 may include a lockout function 22 that interacts with the transfer device 3 to prevent the vial holder 2 from being accidentally pulled out of the transfer device 3 after the vial holder 2 has been activated by the user.

[0023] As shown in FIG. 5, the vial holder 5 is preferably assembled to the transfer device 6 so as to configure the vials 15, 16 upside down in the vertical position. This allows any content (or fluid, liquid, mixture) 23 in the vial to be in direct communication with the vial access members 21, 52 after insertion of the vial holder 5. This also transfers air 24 to the top in this arrangement of the vial. After removal of the vial cap and in order to keep the partition wall 19 of the exposed vial clean before insertion of the vial holder 5, the partition wall 19 of the exposed vial may be fitted into the vial holder 5 to prevent inadvertent contact as shown in FIG. 4. This configuration is applicable to both single vial holder and double vial holder configurations.

[0024] As shown in FIG. 6, the vial holder 2 is preferably mechanically configured within the transfer device 3 with the insertion function 25 so as to operate like an on / off switch, i.e., to have only two states of open and closed like a lighting switch. This can prevent the user from pushing the vial holder 2 halfway into the transfer device 3 and causing the vial access member 21 to break through the partition wall 19 and allowing communication between the content 14 of the vial 12 and the transfer device 3. Further, the vial holder 2 may be coupled to the coupling device 26 to lock the vial holder 2 in the closed position after the vial holder 2 is fully inserted within the transfer device 3 in order to prevent the vial holder 2 from being removed from the transfer device 3 after insertion.

[0025] As shown in FIG. 7, the transfer device 3 includes an outer housing 28 and defines a vial holder docking region (or first receiving station, vial holder docking station, docking station) 29 and an injection device docking station (or second receiving station) 30 (for a removable injection device). In the illustrated structure, the vial holder docking region 29 and the injection device docking station 30 are on opposite sides of the outer housing 28 of the transfer device.

[0026] As shown in FIG. 7, the transfer device 3 may comprise an outer housing 28 that is integrated with the packaging 31 of the system. The outer packaging 31 may basically form the bottom and side walls of the outer housing 28 of the transfer device. All the operating steps in the use of the system until the removal of the injection device occur within this packaging 31. This can reduce costs and improve user-friendliness. Further, by incorporating all the transfer devices 3 into the packaging 31, user errors that may occur when the user is required to remove the transfer device 3 from the packaging 31 can be eliminated. The packaging 31 may include a plastic tab or tray containing the system. Furthermore, the packaging 31 may include everything within the scope of a transport carton 32 that houses the entire system.

[0027] As shown in FIG. 7, the transfer device 3 comprises a vial holder docking region 29 that may include an extended vial access member (or piercing member) 21. This vial access member 21 may be configured as a pointed or blunt cannula or needle. As shown in FIG. 8, a vial holder 5 with a vial 12 attached is inserted into the vial holder docking region 29, showing that the vial access member 21 pierces the septum 19 of the vial, allowing access to the contents 14 of the vial 12. The vial access member 21 may include a foldable seal 33 to maintain the sterility of the vial access member 21 and the fluid flow path prior to activation. The foldable seal 33 may be attached to the outside of the vial 12 and can seal against the vial access member 21 to maintain sterility prior to activation.

[0028] As shown in FIG. 8, the vial access member 21 of the transfer device 3 may include a multi-lumen tube 34 for communicating with the fluid flow path 35 inside the transfer device 3. The vial access member 21 preferably includes one inlet tube 36 and one outlet tube 37 that allows air or fluid to exit the vial 12. These inlet tube 36 and outlet tube 37 may be separate, distinguishable, and may lead to different fluid flow paths in the transfer device 3. Since the vial 12 is in an upside-down position in the vertical direction, the lumen opening 38 of the vial access member 21 may be oriented such that the opening of the inlet tube 36 is above the opening of the outlet tube 37. This orientation allows the introduction of compressed air or liquid through the upper inlet tube 36 and the discharge of the vial contents 14 through the lower outlet tube 37. Further, the opening of the outlet tube 37 may be located adjacent to the partition wall 19 near the bottom of the vial 12 to put all the contents 14 of the vial 12 into the outlet tube 37 and remove them from the vial 12.

[0029] As shown in FIGS. 9 and 10, after the start of the procedure by the user, the transfer device 6 is preferably automatically configured to transfer the contents 14 contained in the vials 15, 16, (reconstitute if necessary), and perform all the steps necessary to transfer the mixture to the injection device 7. The transfer device 6 is preferably configured to include a propulsion system or a plurality of propulsion systems, such as an electrical (e.g., battery-driven) or mechanical (e.g., spring-equipped) pump, that direct the diluent from the diluent vial 16 into the vial 15 of the injectable powder and direct the contents 14 through the transfer device 6 towards the injection device 7.

[0030] As shown in FIGS. 9 and 10, the transfer device 6 may also include a series of internal fluid flow paths 35 when required to perform the transfer, reconstitution, mixing, dilution or other procedures of the contents 14 and the transfer from the vials 15, 16 in the vial holder 5 to the injection device 7. The fluid flow paths 35 may include flexible or rigid pipes or tubes. These fluid flow paths 35 may also include check valves (filters, flow restrictors or other means) 40 for directing the drug from the vials 15, 16 to the transfer device 6.

[0031] As shown in FIGS. 9 and 10, the transfer device 6 can include a pressure chamber or cylinder of variable volume that has a movable spring-type piston inside and that communicates directly with the internal fluid flow path 35. The volume of each chamber of the variable volume chamber can be defined by the diameter of the chamber and the position of the piston. The initial volume of the first pressure chamber 41 in the transfer device 6 can preferably be set by the manufacturer within the range of 1 to 30 milliliters. The initial contents of the first pressure chamber 41 can preferably include air 45. In the first pressure chamber 41 whose volume is determined and set by the manufacturer, the piston 43 can be moved by a spring (compression spring) 44. The spring-type piston 43 can be of a size and configuration sufficient to generate a static air pressure of 1 to 50 psi in the first pressure chamber 41. The volume of the air 45 depends on the diameter of the first pressure chamber 41 and the stroke position of the piston 43 during operation. This pressure depends on the relative volume of the air 45 displaced by the piston 43 and the force exerted by the spring 44. In other words, the product of the force exerted by the spring 44 and the area of the piston 43 in the first pressure chamber 41 determines the static pressure in the first pressure chamber 41. The force exerted by the spring 44 at the start of the contact height or stroke may be much greater than the force exerted by the spring 44 at the end of the movement. The spring 44 can be of an appropriate size to control the rate at which air is discharged from the first pressure chamber 41 and the rate of transfer of the fluid in the transfer device 6. The first pressure chamber 41 is preferably configured to discharge all of the air 45 from the first pressure chamber 41. Alternatively, the flow restrictor 55 in the fluid flow path (or output passage) 35 of the first pressure chamber 41 can be used to control the rate at which the air 45 jets out of the first pressure chamber 41.

[0032] As shown in FIGS. 9 and 10, the volume of the second pressure chamber 42 can be set by the manufacturer. Alternatively, the filled volume for the second pressure chamber 42 ranges from 0.5 to 30 milliliters and can be set by the user during use with a dosage selection part (or volume control part, dosage indicator) 48. The spring-type piston 46 of the second pressure chamber 42 can be sized and configured to generate a pressure of 1 to 200 psi in the second pressure chamber 42. The dosage selection part 48 allows the user to select a dosage defined for injection by the injection device 7 by setting the volume of the filled second pressure chamber 42. The dosage selection part 48 can be of any suitable configuration. The dosage selection part 48 may be directly coupled to a plunger (or pressure plunger assembly, pressure chamber plunger assembly) 93 movable within the second pressure chamber 42. Once the piston reaches a position consistent with the full volume setting, a trigger 49 within the range of the pressure plunger assembly 93 releases the piston 46 in the second pressure chamber 42. By moving the dosage selection part 48 that determines the position of the plunger 93 to define a full volume equal to the desired injection dosage, the user selects the desired dosage in the second pressure chamber 42 for the second time. Alternatively, the position of the plunger 93 may already be determined in a product consistent with the delivered dosage and the user may operate the device without making dosage adjustments.

[0033] As shown in FIGS. 9 and 10, a transfer device 6 for transfer for a dual vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a first pressure chamber 41 with variable volume, a second pressure chamber 42 with variable volume, a fluid flow path 35, and a check valve 40 for directing air from the first pressure chamber 41 to the first vial 16, directing the contents 23 of the first vial 16 to the second pressure chamber 42, and then to the injection device 7.

[0034] As shown in FIG. 8, complete insertion of the vial holder 5 by the user into the transfer device 6 and subsequent introduction of the vial access member 21 into the interior of the vial 12 through the partition wall 19 allows the release of the trigger 50 of the pressure chamber as shown in FIG. 10.

[0035] As shown in FIGS. 9 and 10, the release of the trigger 50 releases the spring 44 of the first pressure chamber, advances the piston 43 of the first pressure chamber within the first pressure chamber 41, and forces the air 45 within the first pressure chamber 41 to enter the first vial 16 through the fluid flow path 35 inside the transfer device 6 and through the inlet tube 36 of the first vial access member 21. More air 45 is forced from the first pressure chamber 41 and into the first vial 16 by the inlet tube 36, and the air 45 rises to the top of the first vial 16 for its vertical placement within the vial holder 5. The increasing air pressure in the first vial 16 causes the contents 23 within the vial 16 to be ejected by the outlet tube 37 of the first vial access member 21 and by the inlet tube 51 of the second vial access member 52. The contents 23 entering the second vial 15 from the first vial 16 mix with the contents of the second vial 15 containing the liquid or powder agent and exit into the second pressure chamber 42 through the outlet tube 53 of the second vial access member 52. Similarly, in the reconfiguration structure as well, the piston (or plunger, feed plunger) 43 of the first pressure chamber 41 continues to push the mixture of the first contents 23 and air 45 through the first vial 16 into the second vial 15. The increasing air pressure at the top of the second vial 15 causes the reconfigured contents 14 at the bottom of the second vial 15 to be discharged out into the second pressure chamber 42. A "pop-off" or check valve 40 or other type of valve may be present in the outlet tube 53 of the second vial access member 52 in order to allow all of the contents 23 of the first vial 16 to enter the second vial 15 before the contents 14 of the second vial 15 are discharged out into the second pressure chamber 42. The valve does not open until the pressure that coincides with the piston 43 that is pushing substantially all of the air 45 from the first pressure chamber 41. This ensures that the contents 54 of the second vial 15 can fully mix the contents 23 of the first vial 16 before the contents 14 of the second vial 15 exit the second vial 15 and apply pressure to the second pressure chamber 42. Alternatively, a flow restrictor 55 may be used in the fluid flow path 35 to extend the transfer and increase the mixing time.

[0036] As shown in FIGS. 9 and 10, the injectable contents 14 flow from the second vial 15 into the second pressure chamber 42 after reconstitution and fill the second pressure chamber 42 up to the limit allowed for the piston 46, corresponding to the desired dosage selected using the dosage selection section 48 by the user or the manufacturer. When the desired volume of the second pressure chamber 42 is achieved, the trigger 49 of the second pressure chamber releases the spring 47 and forces the piston 46 to advance, discharging the selected amount of contents 14 under pressure into the injection device 7. Calibration of the dosage indicated by the dosage selection section 48 and the actual dosage received by the user may require taking into account fluid losses in the fluid flow path 35 inside the transfer device 6. The injection device 7 is now filled and ready to be removed from the transfer device 6.

[0037] As shown in FIGS. 11 and 12, another transfer device 3 within the single vial system 1 is provided that simply transfers the contents 14 from one vial 15 to the injection device 7 without performing mixing. This another transfer device 3 includes a vial holder 2 having a single vial 15, a pressure chamber 56 with variable volume, a fluid flow path 35, and a check valve 40 for directing the contents 14 from the vial 15 to the injection device 7. The inlet tube 36 of the vial access member 21 is exposed to the environment 57 to allow air 58 to enter the vial 15. The outlet tube 37 of the vial access member 21 is connected to the pressure chamber 56.

[0038] As shown in FIGS. 11 and 12, the complete insertion of the vial holder 2 into the transfer device 3 by the user allows access to the contents 14 of the vial 15 through the septum 19 of the vial 15, which also induces the release of the trigger 49 of the pressure chamber. The trigger (pressure release trigger) 49 releases the plunger 60 within the pressure chamber 56 that is connected to the retraction spring 61. The retraction spring 61 forces the plunger 60 to draw in and contain the contents 14 from the vial 15 and fill the pressure chamber 56. The specific amount of the contents 14 drawn in by the pressure chamber 56 can be set by the manufacturer by restricting the retraction of the plunger 60. Further, the pressure chamber 56 can be configured to draw in all of the contents 14 from the vial 15 by retracting the plunger 60 to its maximum travel distance. Once the plunger 60 reaches the set position within the pressure chamber 56, it interacts with the dosing trigger 62 that releases the dosing spring 63 to force the contents 14 out of the pressure chamber 56 and into the injection device 7. The check valve 40 can be used to prevent the contents 14 from returning to the vial 15.

[0039] As shown in FIG. 13, another transfer device 6 for a dual vial system 4 that provides mixing and transfer includes a vial holder 5 that includes a first vial 16 and a second vial 15, a pressure chamber 56 of variable volume, a fluid flow path 35, and a check valve 40 for directing the contents 23 of the first vial 16 into the second vial 15 and the resulting contents 14 into the pressure chamber 56. This contents 14 is then transferred back to the second vial 15 and then to the injection device 7. In this embodiment, the inlet tube 36 of the first vial access member 21 is exposed to the environment 57 to allow air 58 to enter the vial 16. The outlet tube 37 of the first vial access member 21 is connected to the inlet tube 51 of the second vial access member 52. The outlet tube 53 of the second vial access member 52 is connected to the pressure chamber 56 of variable volume. The fluid flow path 35 includes a check valve 40 located between the first vial access member 21, the second vial access member 52, and the injection device 7.

[0040] As shown in FIG. 13, complete insertion of the vial holder 5 into the transfer device 6 by the user allows access to the contents 23, 54 of each vial 15, 16 by introduction of the vial access members 21, 52 through the septum 19 of the vials 15, 16. This also induces release of the pressure chamber trigger. The plunger 60 is released within the pressure chamber 56 connected to the retraction spring. The retraction spring draws in and stores the contents 23 from the first vial 16 and forces the plunger 60 to fill the second vial 15. This filling causes mixing of the contents 23 from the first vial 16 and the contents 54 of the second vial 15. The resulting contents 14 from the second vial 15 fill the pressure chamber 56 until all of the contents 23 have been removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 can be adjusted with the check valve 40 or flow restrictor 55. The amount of contents 23 drawn from the first vial 16 can be set in the pressure chamber 56 by the manufacturer. Once the plunger 60 of the pressure chamber 56 reaches its set position within the pressure chamber 56, it interacts with the dosing trigger that releases the dosing spring to force the contents 14 out of the pressure chamber 56 and back into the second vial 15. This is advantageous for further mixing the contents 23 from the first vial 16 and the contents 14 from the second vial 15. When all of the contents 14 have been dosed from the pressure chamber 56, the contents 14 are transferred to the injection device 7. The volume of the pressure chamber 56 can be set larger than the total fluid volume so that additional air 58 is drawn into the pressure chamber 56. The additional air 58 can serve to ensure that all of the contents 14 are transferred to the injection device 7 or are otherwise within the fluid flow path 35. The check valve 40 can be used anywhere within the fluid flow path 35 to prevent the contents 14 from returning to the first vial during transfer of the contents 14 from the second vial 15 to the injection device 7. The flow restrictor 55 can be used anywhere within the fluid flow path 35 to control the mixing time within the second vial 15 prior to transfer of the contents 14 to the injection device 7.

[0041] As shown in FIG. 14, another transfer device 6 for a dual vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a first variable volume pressure chamber 56, a second variable volume pressure chamber 42, a fluid flow path 35, and a check valve 40 that directs the contents of the first vial 16 toward the second vial 15 and the resulting contents 14 toward the pressure chamber 56. The contents 14 are then transferred from the first pressure chamber 56 to the second pressure chamber 42 and then to an injection device 7. In this embodiment, the inlet tube 36 of the first vial access member 21 is exposed to the environment 57 to allow air 58 to enter the vial 16. The outlet tube 37 of the first vial access member 21 is connected to the inlet tube 51 of the second vial access member 52. The outlet tube 53 of the second vial access member 52 is connected to the first variable volume pressure chamber 56. The fluid flow path 35 includes a check valve 40 that exists between the first vial access member 21, the second vial access member 52, the second pressure chamber 42, and the injection device 7.

[0042] As shown in FIG. 14, complete insertion of the vial holder 5 into the transfer device 6 by the user allows access to the contents 23, 54 of each vial 15, 16 by introduction of the vial access members 21, 52 through the septum 19 of the vials 15, 16. This also induces release of the pressure chamber trigger. The pressure chamber trigger releases the plunger 60 within the pressure chamber 56 connected to a retraction spring. The retraction spring draws in and stores the contents 23 from the first vial 16 and forces the plunger 60 to fill the second vial 15. This filling also mixes the contents 23 from the first vial 16 with the contents 54 of the second vial 15. The resultant contents 14 from the second vial 15 fill the pressure chamber 56 until all of the contents 23 have been removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 can be adjusted by the check valve 40 or the flow restrictor 55. The amount of the contents 23 drawn in from the first vial 16 can be set in the pressure chamber 56 by the manufacturer. Once the plunger 60 of the pressure chamber 56 reaches its set position within the pressure chamber 56, it interacts with a dosing trigger that releases a dosing spring to force the contents 14 out of the pressure chamber 56 and back into the second vial 15. When all of the contents 14 have been dosed from the pressure chamber 56 into the second vial 15, the contents 14 are transferred to the second pressure chamber 42 and fill the second pressure chamber 42 to the limit allowed by the piston 46 selected by the user or the manufacturer, which corresponds to the desired dose. When the desired volume of the second pressure chamber is achieved, the trigger of the second pressure chamber releases the second pressure chamber spring and forces the piston 46 forward, discharging the selected volume of injectable contents 14 under pressure into the injection device. The check valve 40 can be used anywhere within the fluid flow path 35 to prevent the contents 14 from returning to the first vial during transfer of the contents 14 from the second vial 15 to the second pressure chamber 42 and the injection device 7. The flow restrictor 55 can be used anywhere within the fluid flow path 35 to control the mixing time within the second vial 15 prior to transfer of the contents 14 to the second pressure chamber 42.

[0043] As shown in FIG. 15, another transfer device 6 for the dual vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a variable volume pressure chamber 56, a dual lumen connector 94, an inlet flow path 95, an outlet flow path 96, and a check valve 40 for directing the contents 23 of the first vial 16 through the inlet flow path 95 towards the pressure chamber 56 during retraction of the plunger 60 within the pressure chamber 56. Forward movement of the plunger 60 after maximum retraction within the pressure chamber 56 causes the fluid contents 23 to flow from the pressure chamber 56 into the second vial 15, where it is mixed with the contents of the second vial 15, and the resulting contents 14 flow into the injection device 7. The check valve 40 within the outlet flow path 96 will prevent the contents 56 of the second vial 15 from being drawn into the pressure chamber 56 during the retraction phase. During forward movement of the plunger 60, the check valve 40 within the inlet flow path 95 prevents the fluid contents 23 within the pressure chamber 56 from being transferred back to the first vial 16. A check valve within the second vial 15 and the fluid flow path 35 from the injection device 7 prevents the mixture from being transferred back from the injection device 7 to the second vial. A flow restrictor 55 can be used anywhere in the fluid flow paths 35, 95, 96 to control the transfer rate of the fluid. Alternatively, the use of the dual lumen connector 94 can be similarly used in the single vial transfer system 1 for withdrawing and advancing fluid from different fluid flow paths.

[0044] As shown in FIG. 16, the pressure chamber in the above-described embodiment can be configured with an outlet port 64 that is deflected or offset from the center in order to utilize gravity, as compared to a normal syringe. When the pressure chamber 59 is filled with the contents 14 during the transfer process, there may be some air 58 that is introduced into the pressure chamber 59 in addition to the contents 14. During the process of discharging the contents 14 from the pressure chamber 59, it may be advantageous to control the order in which the air 58 or the contents 14 are discharged from the pressure chamber 59. For example, if the outlet port 64 of the pressure chamber 59 is oriented downward during the discharge of the contents 14 from the pressure chamber 59, the air bubbles will be directed to the top of the pressure chamber 59, so that all of the contents 14 are discharged and then the remaining air 58 is discharged last. Conversely, if the outlet port 64 of the pressure chamber 59 is oriented upward during the discharge of the contents 14 from the pressure chamber 59, all of the air 58 is discharged first and then the remaining contents 14 are discharged last. This is particularly advantageous when using a hydrophilic or hydrophobic filter to remove unwanted air 58 from the line during the transfer of the contents 14 to the injection device 7.

[0045] The transfer device may use various devices or procedures to enhance mixing. For example, the transfer device may inject a diluent into the drug-containing vial in a swirling manner and / or use or introduce a mixing enhancement member such as a dynamic or static mixer, such as a mixing ball, a boat cone or a propeller, a vibrating injection tube. These techniques can be used in one of the second vial or syringe. Further, the transfer device may have an intermediate chamber between the second vial access member, the outlet tube and the pressure chamber for causing the mixing enhancement techniques and procedures described above. The transfer device may also be configured to move, for example, by rotating an injectable vial, to introduce an injectable drug vial to induce turbulent flow and enhance mixing. In order to increase the transfer time for greater mixing, a flow restrictor may be used in the air or drug flow path.

[0046] As shown in FIGS. 16 and 17, any other feature of the transfer device 3 is a filter 65 in the fluid flow path 35 of the injectable drug for filtering the injectable content 14 to remove particles before being introduced into the injection device 7. The filter 65 can be a membrane, depth filter or other suitable filtering medium with a pore size or effective pore size small enough to remove undesirable fine particles, and the undesirable fine particles can include, but are not limited to, undissolved injectable drugs in situations where the drug injectable by the transfer device 3 is reconstituted.

[0047] As shown in FIGS. 16 and 17, the recovery from the vial 15 of the injectable drug may require or enhance the introduction of air (replacement air) 58 into the vial 15. In another aspect of the present subject matter, the transfer device 3 may include a replacement air flow path or hole 66 that communicates with the interior of the vial to allow the introduction of air (replacement air) 58 into the interior of the vial 15 when the injectable content 14 is drawn in. As discussed above, the vial access member 21 piercing the septum 19 of the vial may have an inlet tube 36 and an outlet tube 37, one for the injectable content 14 to flow from the vial 15 and one for air (replacement air) 58 to flow into the vial 15. The air (replacement air) 58 flows through a fluid flow path 35 in the transfer device 3 that includes a filter 65 such as a membrane or filter (depth filter, sterile filter) 65 having an actual or effective pore size of about 0.22 μm or less for filtering the air (replacement air) 58. Such a pore size is small enough to prevent pathogens from being introduced into the vial 15 by the air (replacement air) 58 and reduces the risk of contamination of the injectable content 14.

[0048] As shown in FIGS. 16 and 17, the transfer device 3 may include an air remover 67 that communicates with a fluid flow path 35 of an injectable content 14 extending from the vial 15 to the injection device 7. Something like the air remover 67 may include other configurations of bubble traps and air gaps in the fluid flow path 35 of the injectable content 14 that remove air 58 from the fluid flow path 35 of the injectable content 14 before the injectable content 14 is introduced into the injection device 7. The air remover 67 may be composed of a hydrophobic filter 6 or a combination of a hydrophobic filter 68 and a hydrophilic filter 69. The hydrophobic filter 68 allows the discharge of air from the transfer device 3 rather than the passage of the content 14. The hydrophilic filter 69 allows the passage of the content 14 rather than particles or air 58. The combination of the positions of the hydrophilic filter 69 within the fluid flow path 35 preferably removes all of the air 58 during the transfer process.

[0049] As shown in FIGS. 18 and 19, the transfer device 6 may have additional features in addition to those described above. One such feature is a connecting device 70 between the dosage selection part 48 and the vial holder docking area 29. This can be, for example, a mechanical interference member 97 that prevents the user from filling the vial into the vial holder docking area 29 until the dosage is selected. Mechanically, the dosage selection part 48 can be connected to the interference member 97 in the vial holder docking area 29, which is normally in a loading prevention position, to prevent the insertion of the vial holder 5 into the vial holder docking area 29 until the dosage selection part 48 is moved to the dosage selection position and to the loading permission position. Of course, in order to administer the injectable drug from a vial containing a single dose of all the injectable drug to be injected or from a single vial, the transfer device does not necessarily need to include the ability to select the dosage.

[0050] As shown in FIGS. 18 and 19, the transfer device 6 may include a connecting member 71 between the transfer device 6 and the injection device 7 to prevent the injection device from being removed before being filled and to indicate that the injection device 7 is ready to be removed from the transfer device 6. Mechanically, the lock pin 72 may be connected to the injection device 7 to prevent the injection device 7 from being removed before it is completely filled by the transfer device 6. The lock pin 72 may be part of the transfer device 6 and may communicate with the piston in the second pressure chamber 42. When the second pressure chamber 42 discharges all the injectable contents 14, this mechanically induces the lock pin 72 to move away from the injection device 7, permitting the user to remove the injection device 7 from the transfer device 6.

[0051] As shown in FIG. 18, the transfer device 6 may include a connecting device for controlling how the injection device 7 is removed from the transfer device 6 between the transfer device 6 and the injection device 7. Mechanically, a flange or other protrusion 73 on the injection device 7 may mechanically connect with a notch in the transfer device 6. This configuration permits a one-way rotation of the injection device 7 relative to the transfer device 6 during removal by the user.

[0052] As shown in FIGS. 18 and 19, the transfer device 6 may include features for locking to prevent the injection device 7 from being activated. For example, a mechanical interference member such as the lock pin 72, an arch, or other means may extend outside the transfer device 6 and mechanically lock the injection device 7 with an actuator or button in the upper position. Alternatively, the mechanical interference member 72 may be a shielding member that covers the entire injection device 7 to prevent access to the injection device 7 on the transfer device 6. The arch or shielding member (mechanical interference member 72) may be part of the transfer device 6 and may communicate with the second pressure chamber 42. When the second pressure chamber 42 has discharged all of the contents 14 into the injection device 7, this mechanically induces unlocking of the arch or shielding member (mechanical interference member 72) and induces it to move away from the injection device 7. This permits access to the injection device 7 and removal from the transfer device 6 by the user.

[0053] Another optional feature of the transfer device is the rapid release of the filling port or the access member between the transfer device and the injection device to allow rapid release from the transfer device of the injection device and prevent the injection device from contacting the transfer device again. After the injection device is filled and ready to remove the device from the transfer device, the user can remove the injection device. The filling tube (or access member) 83 of the transfer device can be a spring that is loaded when the injection device is removed from the transfer device, and the filling tube 83 is lowered into the transfer device by the spring. This prevents inadvertent leakage of the injection device at the filling port 81 and allows rapid release of the filling tube 83 from the filling port 81 of the injection device. This also makes the filling tube 83 inaccessible to the user and prevents the injection device from contacting the transfer device again.

[0054] As shown in FIG. 18, the injection device 7 and the transfer device 6 are preferably configured for removable attachment of the injection device 7. In the present embodiment, after transfer of the injectable contents 14 from the second pressure chamber 42 in the transfer device 6 to the injection device 7 and release of the connecting member 71 on the transfer device 6, the injection device 7 is separated from the injection device docking station 30 of the transfer device 6 for application to the skin of the subject. As described above, another embodiment described herein includes direct transfer from a single pressure chamber of the injectable fluid to the injection device.

[0055] As shown in FIG. 20, the injection device 7 can have any suitable configuration. As previously explained, the injection device can advantageously use one or more of the features of the injection device described in U.S. Patent Application No. 61 / 326,492, filed Apr. 21, 2010, U.S. Patent Application No. 13 / 637,756, filed Sep. 27, 2012, and U.S. Patent Application No. 61 / 704,922, filed Sep. 24, 2012, which are hereby incorporated by reference in their entirety.

[0056] As shown in FIGS. 20 to 22, the injection device 7 has an upper surface 75 and a lower surface 76 and generally comprises a flat, dish-shaped housing 74 that projects an injection needle or cannula when actuated by a user. The upper surface 75 for initiating an injection has an actuating device or button 77 and a transparent portion 80 of the housing 74 for a subject or medical professional to visually inspect an expandable member 78 to confirm the amount of injectable fluid (medicine, injectable drug) 79 within the injection device 7. For example, the user can determine whether the injection has been initiated or completed. More preferably, the expandable member 78 and / or the transparent portion 80 of the housing 74 can be marked with graduations, such as a line mark 127, so that a patient or medical professional can visually determine the amount of remaining injectable fluid 79 with good accuracy, for example, about 50% complete or about 75% complete. Further, the expandable member 78 can itself include or interact with other features of the housing 74 to indicate the amount of remaining injectable fluid 79. For example, when the injection device 7 is filled with fluid 79, the transparent portion 80 exhibits one color, such as green, although not limited thereto. When the fluid 79 of the injection device 7 is emptied, the transparent portion 80 can exhibit another color, such as red, although not limited thereto. During administration, the transparent portion 80 can exhibit a color combination.

[0057] As shown in FIGS. 23 to 25, the lower surface 76 of the injection device 7 includes a filling port 81 and an administration port 82. The filling port 81 is an interface that permits a transfer instrument to fill a filling tube 83 to transfer fluid 79 into the injection device 7. The administration port 82 also includes a fluid channel (internal flow path 86) between the injectable fluid 79 discharged from the expandable member 78 and a needle (administration needle, injection needle) 85. The filling port 81 and the administration port 82 can communicate directly through a fluid channel (internal flow path 86) or can be coupled to a single port.

[0058] As shown in FIGS. 23 to 25, when the injection device 7 is removed from the transfer instrument 6 and the filling port 81 is removed from the filling tube 83, the injection device can preferably include a filling port 81 that includes a check valve 87 to prevent pressurized injectable fluid 79 from leaking out of the injection device 7.

[0059] As shown in FIGS. 23 to 25, the injection device 7 may also have a filling port 81 configured to receive the insertion of a syringe. This syringe may be composed of a luer fitting or a needle. The configuration of the filling port 81 allows for manual filling of the injection device by the user. The transfer device 6 can still be used, but may not be required in this configuration.

[0060] As shown in FIGS. 23 to 25, the injection device 7 may also have an administration port 82 configured to be directly connected to a venous cannula via an attached tube or a standard needle port.

[0061] As shown in FIGS. 23 to 25, the lower surface 76 of the injection device 7 carries an adhesive 88 to temporarily fix the injection device 7 to the skin of the subject until the injection is completed. During removal of the injection device 7, the surface of the adhesive 88 is exposed on the lower surface 76 of the injection device 7 so that it can be used to adhere the injection device 7 to the patient's skin, and the backing 89 of the adhesive tape can be automatically removed. Alternatively, the backing 89 of the adhesive tape may have a tab 90 for the user to manually pull off before adhering the injection device 7 to the skin. Alternatively, this tab may be attached to the surface of the transfer device 6 so that the backing of the tape is automatically removed when the injection device 7 is removed.

[0062] As shown in FIGS. 23 to 25, the injection device 7 may have an adhesive flange 91 of an adhesive tape extending beyond the lower surface of the lower surface (base) 76. The adhesive flange 91 of the adhesive (adhesive tape) 88 can function to relieve strain between the injection device 7 and the skin surface, reducing the risk of the injection device 7 being accidentally removed from the skin. In other words, similar to the strain relief of the same adhesiveness on the wire entering the connection part, the extended adhesive flange 91 acts to distribute the load on both sides of the connection point between the adhesive 88 and the lower surface (base) 76 of the injection device 7 in order to reduce stress concentration at the interface between the adhesive 88 and the skin.

[0063] As shown in FIGS. 23 to 25, the injection device may be configured to have an adhesive flange 91 with a tapered lower surface 98 that presses the adhesive 88 firmly against the skin so that the user can firmly fix the injection device 7 to the skin without further user interference. When pressing the injection device 7 against the skin, using the conformability of the human skin, the tapered lower surface 98 of the injection device 7 effectively presses the flange 91 of the adhesive 88 against the skin, but the exposed surface above the flange 91 has no exposed adhesiveness and thus cannot be attached to that part of the tapered lower surface 98. The user does not need to run a finger around the flange 91 to firmly attach the injection device 7 to the skin, making the method of attaching the adhesive 88 quite simple.

[0064] As shown in FIGS. 23 to 25, the injection device 7 may have a flexible or compliant lower surface 76 instead of being rigid to allow for an improved attachment of the injection device 7 during application.

[0065] As shown in FIGS. 26 to 28, after the injection device 7 is pressed against or adhered to the skin 99, a safety mechanism or lockout mechanism may be automatically released and the injection device 7 is ready for injection. In other words, the injection device 7 is prevented from being activated (locked out) until it is placed on the skin. Alternatively, the user may manually remove a safety mechanism (safety device) 100 such as a safety pin, safety sleeve or collar so that the injection device is ready for injection. The safety mechanism 100 may be induced passively or actively, manually by the user or automatically by the injection device 7.

[0066] As shown in FIGS. 26 to 28, the injection device 7 can be used in combination with an operating device or button 77 and a visual indicator 101 to define the state of the injection device 7 after it has been removed from the transfer instrument. For example, when the button 77 is in the upper position and the indicator 101 is not limited but has a single color such as green, the injection device 7 may indicate that it is ready to start injection. Further, the button 77 may have a side wall 102 that has a different color from the button top 103. When the button 77 is pressed, the user cannot see the side wall 102 of the button 77. This may indicate that the injection device 7 is in use. When the injection of the drug is completed, the injection device 7 may prompt the user to be vigilant. This alarm may be in the form of a visual indicator, an audible sound, mechanical movement, or a combination. The button 77 is ideally designed to give the user audible, visible, and tactile feedback when it appears in the locked-out position. The injection device 7 may indicate to the user that the administration is complete and the full dose has been delivered to the patient by the button 77 being in the upper position and the indicator (indicator window) 101 indicating that the injection device is empty. For example, when the button 77 is in the upper position and the indicator 101 is not limited but shows a different color such as red, the injection device 7 may indicate that the injection has been completed.

[0067] As shown in FIGS. 29 to 31, the injection device 7 may include an operating device or a button 77 that the user presses with the injection device 7 to start the injection. The button 77 may be configured to be a switch for an on / off operation, i.e., to have only two states of open and closed, like a lighting switch. This can prevent the user from pressing the button 77 partway and starting the injection device 7. Once activated, this "lighting switch" type of button 77 will quickly insert the needle 85 into the skin 99 independently of the user's operation of the button 77. Alternatively, the button 77 may have a continuous movement to allow the user to slowly insert the needle 85 into the skin 99. The button 77 may be preferably directly coupled to the needle 85 using an adhesive 104 that makes the button 77 and the needle 85.

[0068] As shown in FIGS. 29 to 31, when the button 77 of the injection device 7 is activated to advance to the first position or depth as shown in FIG. 30, the needle 85 is moved into the skin 99 and, as shown in FIG. 31, is automatically retracted slightly to the position of the second depth. The first depth shown in FIG. 30 is reached by the movement of the button 77 during operation. The first depth can be controlled in direct contact with the base 106 of the injection device 7 by the configuration 105 within the button 77. The final depth of the needle 85 is suitable for subcutaneous injection. Alternatively, the final depth of the needle 85 may be reduced for intradermal injection. Alternatively, the final depth of the needle 85 may be increased for intramuscular injection. Upon reaching the first depth, immediately, the needle 85 is retracted to the second depth as shown in FIG. 31. The retraction distance of the needle to the second depth is in the range of 0.1 to 2 mm. This retraction function is preferred to prevent the needle 85 from being blocked by tissue during the initial insertion process. This tissue interference can require very high pressures to overcome and can interfere with the injection device 7 delivering the drug. The retraction of the needle 85 from the first position to the second position creates a pocket empty in front of the needle tip 107 and makes it possible to reduce the pressure to start the flow of the drug from the needle 85. This pressure reduction for the start of the flow of the drug from the needle is preferred for the injection device 7 to maintain a relatively constant pressure during injection.

[0069] As shown in FIGS. 29 to 31, the injection device 7 may include a needle 85 with a lateral hole 108. As shown in FIG. 31, once the button 77 of the injection device 7 is fully pressed, the needle 85 is fully inserted into the skin 99 through the dosing port 82 to the end and the injection device 7 starts the administration of the injectable drug. Until the button 77 is fully pressed, the lateral hole 108 and thus the lumen of the needle 85 are not in communication with the fluid channel 86 of the dosing port 82. Both the lateral hole 108 and the needle tip 107 are held within the partition wall 109. At the lateral hole 108 and the needle tip 107 held within the partition wall 109, all drug pathways are kept sterile until use. When the button 77 is fully pressed and the needle 85 is in the dosing position, the lateral hole 108 of the needle 85 is in communication with the fluid channel 86 of the dosing port 82 and the injection of the liquid begins.

[0070] As shown in FIGS. 29 to 31, the septum 109 provides the advantage that the needle tip 107 and the lateral hole 108 are sealed from the injectable drug before and after administration. Sealing the needle tip 107 and the lateral hole 108 of the needle 85 at the end of the injection is particularly advantageous for preventing the injectable drug from dripping from the injection device 7, especially after the end of administration and / or after removal from the skin surface. Also, it prevents contaminants from entering the needle holes before entering the skin. The septum 109 can be made of any suitable material that allows it to seal once the needle 85 has made a hole. The material of the septum 109 is preferably silicone. Alternatively, the specific configuration of the septum may be a mixture of different materials including bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber and silicone, but is not limited thereto. Alternatively, the fluid flow path 86 including the administration port 82 can be a rigid plastic injection molded to produce the above-described septum having silicone.

[0071] As shown in FIGS. 29 to 31, the septum 109 of the administration port 82 can protrude slightly into the surface of the skin 99 from the lower surface of the injection device 7 in order to pressurize on the surface of the skin 99 in the injection area. This pressure on the surface of the skin 99 by the administration port 82 after the needle is retracted can remove the injectable drug from coming out of the injection area, which is generally called recoil.

[0072] As shown in FIGS. 29 to 31, the injection device 7 can include a set of spring tabs 110 that engage a button 77 for performing a locking function. As shown in FIG. 29, the spring tabs 110 are deflected to lock into a notch 111 within the button 77 in order to position the button 77 in a first upper or pre-injection position. The shape of the notch 111 and the spring tabs 110 serve to create the operation of the illumination switch described above. This operation of the illumination switch is achieved by the replacement of the button 77 with respect to the spring tabs 110 and the fitting of the surface of the notch 111.

[0073] As shown in FIGS. 29 to 31, the injection device 7 may include a spring tab 112 that interacts with a button 77 within the injection device 7 to perform a locking function. When the button 77 is actuated to a first depth and is slightly retracted to return to a second depth or the administration position, a cut-off function 113 within the button 77 permits the spring tab 112 to hold the button 77 in the administration position until the injection device 7 completes administration.

[0074] As shown in FIGS. 32 to 33, in order to sense when all of the fluid 79 has been released from the expandable member 78 and the injection device 7 has completed administration, the injection device 7 may include a delivery indicator or an empty indicator 114. The empty indicator 114 may be configured to have a slot or other opening 115 in the outlet port through which the expandable member 78 slides when the expandable member 78 is in a vented state after all of the fluid has been released. The empty indicator may have two states. As shown in FIG. 32, when the expandable member 78 is filled with the fluid 79 and not received within the slot or opening 115, the empty indicator may be in a first position or a deflected-out state. The first state may be described as not empty when the diameter of the expandable member 78 is greater than its minimum by the remaining fluid 79 contained therein. As shown in FIG. 33, when the expandable member 78 is partially or fully received within the slot or opening 115, the empty indicator 114 may be in a second position or a deflected-in state. The second position may be described as the empty state of the expandable member 78 when the diameter is at a minimum.

[0075] As shown in FIGS. 32 - 33, the injection device 7 may include a mechanism for automatically retracting the needle at the end of administration. This mechanism includes a direct connection between the spring tab 112, the button cut - off function 113 and the air indicator 114 as described above. The expandable member 78 is filled with fluid 79, and when the button 77 is pushed from the first injection - before position to the second administration position as shown in FIG. 33, the cut - off function 113 of the button 77 allows the spring tab 112 to hold the button 77 in the administration position until the injection device 7 completes administration. The spring tab 112 can also be directly coupled to the air indicator 114 which is in the first position or deflected outwardly, of course. The movement of pushing the button 77 to the second or administration position allows the spring tab 112 to deflect or apply an initial load to the post function 116 in the button 77, prompting the air indicator 114 to deflect to the second or inward position. However, since the expandable member 78 is initially filled with injectable fluid 79 and has a large diameter, as shown in FIG. 32, the air indicator 114 cannot move to the second or inward - deflected state. After the button 77 is pushed, the fluid 79 begins to be released through the needle from the expandable member 78 as described above. Once the expandable member 78 has released all of the fluid 79 and is at a minimum diameter, the air indicator 114 (under the initial load from the spring tab 112) moves to the second or inward - deflected state as shown in FIG. 33. The spring tab 112, which is also directly coupled to the air indicator 114, moves with the air indicator 114. This movement releases the spring tab 112 from the cut - off function 113 in the button 77 to raise the button 77 (and the needle) to the final or post - injection position after administration is complete, as shown in FIG. 34.

[0076] As shown in FIG. 34, when the injection is completed and the button 77 is released and urged by the return spring 118 to return to the final or post-injection position, the lockout spring tab 117 can interact with the button 77 within the injection device 7 to perform a locking function. The height of the button 77 relative to the top of the injection device 7 in the final or post-injection position (FIG. 34) may be higher than in the pre-injection position (FIG. 29). The end of the lockout spring tab 117 moves within the housing 74 towards the outer diameter surface 119 of the button 77 to lock the button 77 in the upper or post-injection position so that the button 77 does not start to operate again.

[0077] As shown in FIG. 34, the injection device 7 may include a return spring 118 that interacts with the button 77 to deflect the button to the first upper or post-injection position. When the button is lowered to the second depth or administration position, the return spring 118 is compressed, causing further deflection or preloading. At the end of the administration period, after the administration is completed as described above, the button 77 is unlocked from the second depth or administration position (FIG. 31) and raised to the final or post-injection position. It is the deflection of the return spring 118 that forces the button 77 to rise to the final or post-injection position.

[0078] As shown in FIGS. 34 - 35, simultaneously with the removal of the injection device 7 from the skin 99, the injection device 7 is preferably locked out. This prevents non-destructive access to the needle or reuse of the injection device 7. The injection device 7 may inform the user that a full dose has been delivered. This indication may be in the form of a visual indicator, an audible sound, mechanical movement, or a combination thereof.

[0079] As shown in FIG. 35, simultaneously with the removal of the injection device 7 from the skin 99, the dressing 120 may be released from the injection device 7 and remain on the surface of the skin 99. This can be affected by the use of an adhesive for the dressing portion that adheres more strongly to the skin than the adhesive that attaches the dressing to the injection device 7. When the housing is thus lifted from the skin, the dressing 120 remains over the injection area as described in U.S. Patent No. 7,637,891, which is hereby incorporated by reference in its entirety, and U.S. Patent Application No. 12 / 630,996, filed December 4, 2009.

[0080] As shown in FIGS. 36 - 39, the injection device 7 may preferably include an expandable member 78, a filling port 81, and a manifold 121 assembled to a dosing port 82, providing direct fluid communication between the expandable member 78, the filling port 81, and the dosing port 82 of the injection device 7. As described above, the manifold 121 may be assembled to the expandable member 78 and configured at an end such that the expandable member 78 has a large diameter to facilitate filling and the release of all fluid 79 outside the expandable member 78. To allow fluid to flow in and out of the expandable member 78, the manifold 121 may preferably include an internal flow path 122. The manifold 121 may be configured with a filter 123 to filter the injectable fluid 79 to remove particles before and after being introduced into the expandable member 78 within the flow path 122 of the injectable fluid. The filter 123 may be a membrane, depth filter, or other suitable filtering medium with a pore size or effective pore size small enough to remove undesirable fine particles. Without limitation, undesirable fine particles may include undissolved injectable fluid 79 in situations where the injectable fluid 79 is reconstituted by a transfer device. The manifold 121 may also be configured with a filter 123 for removing or venting air. Such a filter (air vent filter) 123 may include a bubble trap, or other configured air gap, within the flow path 122 of the injectable fluid to remove air from the flow path 122 of the injectable fluid before it is introduced into the expandable member 78. This filter 123 may be configured as a hydrophobic filter or a combination of a hydrophobic filter and a hydrophilic filter. The hydrophobic filter allows air to be discharged from the transfer device without allowing liquid to pass through. The hydrophilic filter allows liquid to pass through without allowing fine particles or air to pass through. The filter 123 may optionally also include a check valve to discharge trapped air. Alternatively, the filter 123 may be located at any position in the fluid flow path from the filling port 81 to the needle 85. For example, the most downstream point in the fluid flow path is the end 128 of the expandable member 78. The internal mandrel 124 may be connected to the end 128 of the expandable member 78. During filling of the injection device 7, the filter 123 may be integrated at this downstream point to discharge trapped air.Furthermore, the mandrel 124 may include slots along its length that communicate with a downstream filter 123 that helps to expel air during the filling process.

[0081] As shown in FIGS. 36 - 39, the injection device 7 may include a strong expandable member 78 such as an elastic balloon or airbag. The specific configuration of the expandable member 78 may desirably be silicone. Alternatively, the specific configuration of the expandable member 78 may be a mixture of different materials including but not limited to bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber and silicone. In addition to this, the expandable member 78 may be coated to improve its surface properties. The coating may include parylene, silicone, Teflon and fluorine gas treatment. Alternatively, the expandable member 78 may be made from a thermoplastic elastomer.

[0082] As shown in FIGS. 36 - 39, the injection device 7 can include a strong expandable member 78 through which fluid 79 is transferred under pressure. This expands the expandable member 78, and the repulsive force of the expandable member 78 creates a pressure that tends to release the fluid 79. As described above, the pressure chamber of the transfer device (or other pump or pressurizing means used in the transfer device) transfers the fluid 79 to the injection device 7 under pressure. Introducing the fluid 79 into the expandable member 78 under pressure causes it to expand in diameter and length. This example is like blowing up a long, thin balloon. The volume range of the injection device 7 can be from 0.5 to 30 milliliters. When expanded, as described above, the strong expandable member 78 exerts an expulsion pressure in the range of 1 - 200 psi by the fluid 79 contained in the expandable member 78 so that when induced by the user by pressing the button, the injection device 7 is automatically ready to administer the fluid 79. Thus, the transfer device, as described above, does not transfer a measured amount of fluid 79 (mixed, diluted, filtered as necessary) only for transfer to the injection device 7, but rather, when activated by the user, causes or provides a pressure that has the force to move the injection device 7 (by expanding the strong expandable member 78) so that the injection device 7 is automatically ready to expel the fluid 79 under the pressure exerted by the strong expandable member 78.

[0083] This aspect of the transfer device (simultaneous transfer and load) is particularly beneficial. While the above applications show the injection device 7 in a pre-filled or loaded state for injection of the fluid 79 when the injection device 7 is activated, in the present disclosure, until administration of the injectable fluid 79 is required, the injection device 7 remains empty and the expandable member 78 is in a more relaxed and unfilled state, i.e., unloaded or non-filled. Only then is the injectable fluid 79 mixed or processed as needed and introduced into the injection device 7 to inflate the expandable member 78 to a filled (loaded) state. In the present disclosure, the drug is stored in an initial sealed container (vial) until use. Since the fluid 79 is typically injected within seconds to hours after being transferred from the vial to the injection device 7, the shelf life of the drug and the compatibility of materials in the fluid flow path within the injection device 7 are not major issues. The challenges and costs of designing the injection device 7 to select materials for the long-term shelf life of a pre-filled injection device 7 are considerably reduced.

[0084] As shown in FIGS. 36-39, the present subject matter can, as described above, utilize the features of the injection device 7 described in patent applications incorporated herein by reference. However, as illustrated, the expandable member 78 used in the injection device 7 here may desirably take the form of, for example, a flat spiral or an elongated balloon or airbag arranged in a spiral configuration. As described above, the injection device 7 includes a circular housing (outer housing or injection housing) 74 in which a spiral slot or recess (or slot, helical channel) 125 is made. The expandable member (elongated balloon or airbag) 78 is placed within the recess 125, one end communicating directly or indirectly with the needle 85 through a fluid flow path 122, and the other end communicating directly or indirectly with the administration indicator 101. While contributing to the unobtrusive configuration of the injection device 7, the elongated spiral configuration gives the expandable member 78 a significant volume for the desired amount of fluid 79. In other words, by utilizing a relatively long expandable member 78 with a fairly high length-to-diameter ratio, it can be achieved with minimal force where very high pressures and volumes are required. Moreover, by varying the fill length, the volume of the expandable member 78 can be varied without significantly changing the pressure / volume curve of the expandable member 78.

[0085] As shown in FIGS. 36 - 39, one of the other aspects used in other subject matter described in U.S. Patent Application No. 61 / 704,922, filed Sep. 24, 2012, is the use of an insert or plug or mandrel 124 for prestressing the expandable member 78 to a slightly expanded position when not filled, within the expandable member 78. Thus, as shown in FIGS. 38 and 39, when the expandable member 78 releases the fluid 79, it shrinks or collapses while still being extended or under pressure and continuing to exert pressure on the internal liquid. This better ensures that all or substantially all of the fluid 79 is completely released from the injection device 7. The shaft or mandrel 124 can be an expandable member filled with fluid as needed. This takes into account a variable - sized mandrel 124. Alternatively, the expandable member 78 can have a sufficiently small internal volume (small diameter) when not under pressure so that substantially all of the fluid 79 is released without the need for an internal shaft or mandrel 124. Additionally, the expandable member 78 can be flattened / pulled by "wrapping" its surface like a cylindrical wall 134 within the injection device. The prestress created within the expandable member 78 will serve to remove any remaining fluid volume left inside.

[0086] As described above, there are several different ways to expand and / or bow the expandable member 78. Returning to FIG. 34, one way is to design the expandable member 78 to have a thicker wall region 126 in one area around the circumference of the expandable member 78 that expands circumferentially around the expandable member 78. Alternatively, the region (separating element) 126 can be attached along the length of the expandable member 78 to effectively stiffen the expandable member 78 at the circumferential portion where the expandable member 78 is expanded in an arcuate shape. Returning to FIG. 36, another way is to use internal features such as slots or recesses 125 in the housing 74 of the injection device 7 that guide the expandable member 78 around, for example, the circumference of a circular or helical passage. These features can interact with the expandable member 78 in several ways, and most simply, the outer shape of the expandable member is constrained by the recess 125 in the housing 74 of the injection device 7. By applying oil to the outer surface of the expandable member 78, or by inserting the expandable member 78 into a low spring rate spring that limits the outer diameter of the expandable member 78 but does not constrain the length, the friction between the expandable member 78 and the inner surface recess 125 of the housing 74 can be reduced.

[0087] As shown in FIGS. 36 - 39, the elongate expandable member 78 may desirably be configured to expand along an arc with a predetermined tube diameter without the aid of a wall or guide within the range of the injection device. Looking at a cross - sectional view of the elongate expandable member 78 and returning to FIG. 34, a thicker wall region 126 of a small portion of the circumference of the expandable member 78 may be added to expand the elongate expandable member 78 in an arcuate shape as described above. The arcuate expandable member 78 increases in length due to an increase in internal pressure and volume, and the thicker region 126 is less deflected than the thinner regions.

[0088] As shown in FIG. 36, the arcuate expandable member 78 expands in length in an arcuate shape so as to deflect the area inside the circle in order to direct it towards the heavier wall thickness area 126 and below. Increasing the wall thickness area 126 of the expandable member 78 within the small area 126 around the circumference effectively continues to reduce the radius of the arc of the expandable member 78. The increase in the wall thickness area 126 can be achieved by forming or extruding the arcuate expandable member 78, or by joining small pieces of material to the area 126 on one side of the expandable member because that part of the wall area 126 causes it to extend at a slower rate. And thereby, as described above, the expandable member 78 is expanded in an arcuate shape.

[0089] As shown in FIG. 37, an element such as an indicator 101 can be attached to the end of the expandable member 78. And it is forced to follow a guide path within the recess 125 on the inner surface of the housing 74. Alternatively, the expandable member 78 can be prestretched and flattened around a circular diameter within an injection device 7 such as a wall 134 so that there is no change in the length of the expandable member. Alternatively, a straight or curved mandrel 124, which is longer than the non-extended expandable member, can be used to pull the expandable member into a circular shape within the injection device 7 before filling. Alternatively, the mandrel 124 can be used as a visual indicator showing the state of the injection device 7 and the progress of the injection. The mandrel 124 can be colored so that it can be easily seen by the housing.

[0090] As shown in FIGS. 36-39, fluid 79 is injected into expandable member 78 by a transfer device, and expandable member 78 is expanded to a specific outer diameter controlled by the configuration of recess 125 on the inner surface of housing 74. In this way, all of the length of expandable member 78 can be filled with a known dose of medicine, and the outer diameter is known at each longitudinal location along expandable member 78. It is desirable to fill and empty expandable member 78 along its length in a controlled manner, from one end to the other, such that expandable member 78 is completely emptied and the fluid 79 within expandable member is easily and accurately measured. Visually, to assist in determining how much fluid 79 is within expandable member 78, scale markings can be printed on expandable member 78, such as a syringe, to indicate the volume remaining within expandable member 78. As described above, and as shown in FIGS. 21-22, expandable member 78 and housing 74 can be transparent to allow the user to see fluid 79 and the volume remaining within injection device 7. Alternatively, scale markings 127 can be printed on housing 74 to indicate the volume remaining within expandable member 78.

[0091] As shown in FIGS. 36 - 39, according to the aspects of the present subject matter described above, the injectable fluid 79 is preferably discharged step - by - step from the distal end 128 of the extended expandable member 78 towards the proximal end (proximal outlet port end) 129. The proximal end 129 of the expandable member is closest to the needle 85 or cannula. This allows the user to visually confirm or estimate the injection state, with the help of a transparent portion (window, indicating window, transparent area or other indicator) 80 on the housing 74 or a scale mark 127 on the expandable member 78, or alone. The step - by - step discharge can be achieved in various ways. For example, the injectable fluid 79 exits the expandable member 78 in a manifold 121 disposed at the proximal end 129 of the preferably extended expandable member (e.g., balloon or airbag) in the area 130 of the proximal outlet port. The wall thickness of the expandable member 78 varies and can be constant, increasing along the length from the distal end 128 towards the proximal end 129, or step - by - step. Due to the constraint by the wall of the recess 125 in which the expandable member 78 is placed, the expandable member 78 expands to a substantially single diameter along the length with the injectable fluid 79. However, the thicker wall at the distal end 128 of the expandable member 78 exerts a greater constraint on the injectable fluid 79, and the thinner wall at the proximal end 129 causes the diameter to fold or contract during the discharge of the injectable fluid 79. The expandable member 78 is gradually folded from the distal end 128 towards the proximal end 129 as the wall of the expandable member 78 becomes thicker along the length from the distal end 128 towards the proximal end 129. Since the thickness of the expandable member 78 preferably increases substantially uniformly from the proximal end 129 towards the distal (or closed) end 128, the tightening force of the wall of the expandable member 78 increases when inflated and increases substantially uniformly along the length from the proximal end 129 to the distal end 128 of the expandable member 78. Thus, when the injectable fluid 79 is discharged to the subject, the expandable member 78 gradually folds in diameter and also contracts in length, and the diameter - wise folding and length contraction are preferably visible to the user as described above. The distal end 128 of the expandable member can be connected to an indicator (movable indicator element) 101 of the injection device 7 that follows the contraction of the length of the extended expandable member 78.This indicator 101 is preferably visible to the user through the housing 74 and indicates the state of the injection device 7 and the progress of the injection. Alternatively, the expandable member 78 is formed with a constant wall thickness and is prestressed during manufacture to be filled from its proximal end 129 to its distal end 128 and to be folded or deflated in a stepwise manner from its distal end 128 to its proximal end 129 as described above.

[0092] As shown in FIGS. 36 - 39, the extended expandable member 78 of the injection device 7 can be configured to have a region 130 of the expandable member 78 adjacent to the proximal end 129 that first fills and last folds during the filling and discharge of injectable fluid 79 from the injection device 7. In other words, it is advantageous for the region 130 of the most proximal outlet port end of the expandable member 78 to first fill with the injectable drug during the filling of the injection device 7 by the transfer device. Further, during the administration of the injectable fluid 79 from the injection device 7, it is advantageous for the volume of injectable fluid 79 remaining until the end to be in the region 130 of the most proximal outlet port of the expandable member. There are several advantages to the above-described configuration. The region 130 of the proximal end of the expandable member 78 can have a thin wall that remains inflated even under a lower pressure than the rest of the expandable member 78. The region 130 of the expandable member 78 will surely remain inflated until all of the injectable fluid 79 has been discharged from the other parts of the expandable member 78. As discussed above, the region 130 can be directly coupled to the empty indicator to give a fill or empty indication. Further, as discussed above, this region 130 can be mechanically coupled to the empty indicator to cause the automatic retraction of the button 77 and the needle 85 upon completion of the discharge of the injectable fluid 79.

[0093] As shown in FIGS. 36 to 39, in another or further variant of the wall thickness region 126 of the expandable member 78, the extended internal shaft or mandrel 124 within the expandable member 78 gradually (constantly or stepwise) decreases the cross-sectional area and length of the expandable member 78 along the proximal end 129 to the distal end (closed end) 128 of the expandable member 78. Further, the manifold 121 for attaching the expandable member 78 to the injection device 7 may also be configured to have a large-diameter region 130 at the proximal end 129 of the expandable member 78. The large-diameter region 130 of the mandrel 124 or the manifold 121 at the proximal end 129 of the expandable member 78 ensures that the expandable member 78 first fills this region 129 with the injectable fluid 79. In other words, the expandable member 78 is held at the proximal end 129 with an almost filled diameter by the large-diameter region 130 of the mandrel 124 or the manifold 121. The fluid 79 first fills the expandable member 78, first reaches the diameter of the large-diameter region 130, and then gradually fills from the proximal end 129 towards the distal end 128 along the length of the expandable member 78 as described above.

[0094] As shown in FIGS. 36 to 39, as previously described, during the administration of the injectable fluid 79 from the expandable member 78, the diameter of the expandable member 78 gradually continues to fold at the distal end (like a long thin balloon shrinking) from the distal end 128 towards the proximal end 129 until all the fluid is released from the expandable member 78. The large-diameter region 130 of the mandrel 124 or the manifold 121 at the proximal end 129 of the expandable member 78 provides the same benefit during the administration of the injectable fluid 79 (as described above for filling). This large-diameter region 130 ensures that the fluid 79 remaining last within the expandable member 78 is contained within this region 130 and is administered therefrom. As discussed earlier, the region 130 is directly coupled to the empty indicator to also provide a fill or empty indication for the automatic retraction of the button 77 and the needle 85 upon completion of the release of the injectable fluid 79.

[0095] [Operation and Method] As shown in FIGS. 40 - 42, the sterile injection device 7 is attached to the transfer device 3 within a covered tray 132, and a separately packaged vial holder 2 with a filled vial is provided in a carton 131. The user places the carton 131 on a clean, flat surface. To expose the assembly of the transfer device 3 and the vial holder 2, the user opens the lid 133 on the carton 131. The user removes the cover from the tray 132 of the transfer device 3 to expose the transfer device 3 and the injection device 7. The user is instructed to leave the transfer device 3 in the carton 131 and remove only the injection device 7 when so noted.

[0096] As shown in FIGS. 43 - 44, during use, the user removes the vial holder 2 assembly from the carton 131. Then, using the attached cap - remover, the user removes the vial cap from the vial. The user inserts the vial holder 2 into the transfer device 3. The user presses the vial holder 2 with the vial 16 attached to the transfer device 3 to move the system 1. This does three things in the illustrated embodiment. First, it captures the vial holder 2 with the vial 16 mounted in a lower position within the transfer device 3. Then, by introducing an access member through the septum of the vial, it automatically initiates fluid communication between the vial 16 and the contents 23 of the transfer device 3. Thirdly, it begins mixing (if necessary) and advances the sequence of the transfer device 3. This sequence occurs automatically and requires no further input by the user to initiate or proceed.

[0097] As shown in FIGS. 45 to 47, in the dual vial system 4 where mixing is required, the user may have the ability to adjust the delivery dose. The dose selection section 48 is moved from the initial position shown in FIG. 46 to the final delivery volume position in FIG. 47. Here, the vial holder 5 is to be freely pushed in by the user to initiate mixing and transfer. First, the diluent fluid is transferred from the diluent vial and brought to the powdered lyophilized injectable vial. The fluid is brought to the powder vial in such a way that all the powder is removed as well when the fluid is transferred from the vial. Mixing the diluent and the powder may occur completely in the powder vial or may be completed with the transfer device. Static or dynamic mixing elements may be incorporated into the transfer device or may be provided to the powder vial and the diluent in the transfer device for adequately formulating the powdered drug or other injectable drug. Mixing may take up to several minutes to complete. Mixing is done in the gentlest direction possible to minimize foam / effervescence and shear stress. Mixing is done in such a way that the powder is completely mixed and there are no pieces. An in-line filter, valve or other means may be used to remove pieces or air. An indicator may be on the transfer device to show that mixing is progressing.

[0098] As shown in FIGS. 45 to 47, in the system of the dual vial holder 5, the reconstituted solution is added to the powder vial or the transfer device 6, and the set amount of the solution determined by the manufacturer or the setting by the user is automatically changed in the pressure dosing chamber. Then, this set volume is automatically transferred to the injection device 7. To facilitate the transfer of the maximum percentage of the drug to the injection device 7, the fluid flow path volume between the tube, pipe valve and any other vial and the transfer device 6 is minimized.

[0099] As shown in FIGS. 48 to 50, once the required dose has been delivered to the injection device 7, the transparent parts 80, 101 of the injection device 7 allow the user to see the mixed solution in order to confirm complete mixing. Ideally, the user should be able to visually check all the drug volume within the injection device 7. There may also be an indicator (index), such as a relative filling gauge, 101 to indicate that the correct dose has been delivered to the injection device 7. Then, the completion of mixing and transfer to the injection device 7 allows the injection device 7 to be "opened like a tablet" and removed from the transfer device 3, 6 or the injection device docking station. The injection device 7 may indicate to the user that it is in a ready state by having the button 77 in the up or ready position and the transparent parts 80, 101 indicating that the injection device is filled.

[0100] As shown in FIG. 50, by twisting or removing the injection device 7 from the transfer device 3, the user may disconnect the injection device 7 from the transfer device 3. During removal of the injection device 7, the adhesive tape backing may be automatically removed, exposing an adhesive surface on the bottom of the injection device used to adhere the device to the patient's skin. Alternatively, the tape liner may have a tab that the user can pull to move the device manually to the skin before attachment.

[0101] As shown in FIG. 51, the user attaches the injection device 7 to the skin 99. There may be an adhesive on the bottom of the injection device 7 to allow for adhesion to the skin 99 surface and hands-free operation. The adhesive may spread beyond the contour of the injection device to allow the user to firmly attach the tape to the skin. Alternatively, the user may hold the injection device 7 against the skin 99 during injection.

[0102] As shown in FIGS. 51 to 53, the user removes the safety mechanism (safety device) 100 and presses the button 77 of the injection device 7 to start the injection. Once the button 77 of the injection device 7 is fully pressed, it is properly locked, and the needle is fully inserted into the patient, and the injection device 7 starts to deliver the injectable medicine. The injection device 7 may give an alarm to the user indicating that the injection of the medicine has started. This alarm can be in the form of visual instructions, audible sounds, mechanical movements or combinations thereof. The injection time can range from a few seconds to several hours. The injection device 7 can indicate to the user that it is being administered by having the locked button 77 and the indicator (indicator window) 101 in the lower position indicating that the injection device 7 has less than a full dose. The injection device 7 preferably has a transparent part 80 that allows the user to easily measure the amount of medicine remaining in the injection device 7.

[0103] As shown in FIG. 54, when the injection of the medicine is completed, the user is warned. This alarm can be in the form of visual indicators, audible sounds, mechanical movements or combinations thereof. The injection device 7 can indicate to the user that the administration is completed, both tactilely with an audible sound and by the button 77 moving to the lock-up position, and by the indicator (indicator window) 101 indicating that the injection device is empty. At the end of the administration, the needle is automatically retracted to the locked position inside the injection device 7.

[0104] As shown in FIG. 54, simultaneously with the removal of the injection device 7 from the skin 99, the dressing 120 is released from the injection device 7 and may remain on the skin surface 99. Simultaneously with the removal from the skin 99, the injection device 7 is preferably locked out, preventing non-destructive access to the needle or reuse of the injection device 7. The injection device 7 can inform the user that a full dose has been delivered. This indication can be in the form of visual instructions, audible sounds, mechanical movements or combinations thereof.

[0105] In accordance with a further aspect of the subject matter, when performing an injection with a syringe and needle that is supposed to be injected under the skin, it is desirable to know whether the needle is properly placed within the skin area or inappropriately placed within the vascular area. For a user performing an intradermal (ID), subcutaneous (SC), or intramuscular (IM) injection, it is common to pull back on the plunger to cause a pressure drop within the syringe to see if visible blood comes up onto the needle in the syringe. If blood is visualized, this means that the tip of the needle is in a blood vessel. Injectable medications for injection under the skin are specifically indicated to not be injected into veins in particular. Blood aspiration using a syringe and needle can be performed by anyone with sufficient training in general techniques. However, more medications are being presented in automated injection devices and there is no ability to manually aspirate in this type of system. Once the injection device is placed on the skin and the needle is fired, there is no way for the user to know whether the needle is properly placed within the skin area or inappropriately placed within the vascular area. Accordingly, there is a need for a blood aspiration device and method within an automated injection device.

[0106] As shown in FIGS. 55-56, injection device 7 may be slidable within the range of partition wall 109 where needle 85 with lateral hole 108 acting with button 77 advances into skin 99. Button 77 may have viewing window 160 on button top 103 that is in fluid communication with proximal end 161 of needle 85. Button top 103 may include cavity 162 for blood 159 to accumulate and be visible to the user through viewing window (button window) 160. Cavity 162 may include central hole 163 that permits fluid communication with proximal end 161 of needle 85 through lumen (needle lumen) 165. Outer wall 164 of cavity 162 is created by button top 103. Further, some of outer wall 164 may include hydrophobic filter 166. In this configuration, proximal end 161 of needle 85 is at atmospheric pressure. If contents 14 or blood 159 move over lumen 165 inside needle 85, it exits proximal end 161 of needle 85 and fills cavity 162. Until all of air 167 in cavity 162 is displaced, air 167 in cavity 162 is easily replaced by hydrophobic filter 166 and it is filled with contents 14 or blood 159. Here, contents 14 or blood 159 cannot permeate hydrophobic filter 166, flow of contents 14 or blood 159 stops and can be easily seen by the user through viewing window 160 on button top 103.

[0107] As shown in FIG. 56, simultaneously with actuation (or pushing) of button 77, needle 85 and button 77 move to an initial position or depth as shown in FIG. 56. At this initial position or depth, lateral hole 108 is covered by partition wall 109 and thus lumen 165 of needle 85 is not in communication with the fluid channel of dosing port 82. If needle tip 107 is within vein 158 at the first position or depth, the pressure within vein 158 causes blood 159 to rise towards proximal end 161 of needle 85 through lumen 165, filling cavity 162 with blood 159, which is visible through viewing window 160 on button top 103 of button 77, providing a way to determine whether needle 85 of injection device 7 is within vein 158.

[0108] As shown in Fig. 57, the insertion of a needle into tissue can generally be divided into four stages. These include non-contact, boundary replacement, tip insertion, and shaft insertion. During boundary replacement, the tissue boundary in the contact area is deflected by the load applied by the needle tip, but the needle tip has not penetrated the tissue. The skin boundary follows the needle tip in the contact area up to the maximum boundary replacement point where the needle tip begins to penetrate the skin. After the needle tip has penetrated the skin, the shaft is inserted into the tissue. Even after the insertion of the tip and shaft, the boundary surface of the skin in the contact area does not return to its original non-contact state but remains displaced by a distance x. The amount of boundary displacement x is a function of several parameters including the needle diameter, the shape of the needle tip, the friction of the needle shaft, the needle insertion speed, and the physical properties of the skin. The skin boundary displacement x in the contact area is characteristic of a needle-based injection device. This is because it affects how much the needle penetrates the skin, and thus the actual needle penetration depth can be reduced by the magnitude of the boundary displacement x. If the boundary displacement x is intentionally induced by stretching or preloading the skin outside the contact area prior to the needle tip, then during insertion there will be no further boundary displacement by the needle tip or shaft, and the needle tip depth will be defined as expected. This intentional displacement is advantageous in that the amount of needle penetration into the tissue is not affected by changes in the boundary displacement. If the boundary displacement is not intentionally induced at the skin surface prior to the insertion of the needle tip, the actual needle penetration depth into the skin is not specifically known. This is because some of the needle length is outside the skin due to the naturally occurring boundary displacement x (due to the above parameters) as shown in Fig. 57. On the other hand, when the maximum boundary displacement is induced in the contact area, the actual needle penetration depth will not change with changes in the above parameters including the needle diameter, the shape of the needle, the friction of the needle shaft, the needle insertion speed, and the physical properties of the skin.

[0109] As shown in FIG. 58, the injection device 7 may comprise a skin boundary line replacement extension or structure such as an extension 138 included in the lower surface 76 at or around the administration port 82 or as part of the administration port 82. When the injection device 7 is attached to the skin 99, the extension 138 projects out of the surface of the skin 99 and causes displacement of the skin membrane 99 in this contact area 139. During actuation of the button 77 from the pre-injection state to the first position, the needle 85 advances into the skin 99 from the injection device 7 through the administration port 82 and / or the extension 138 in order to start drug administration. For the reasons described above, when the needle 85 advances from the injection device 7, the needle tip 107 does not cause a further boundary displacement 141 (already deliberately induced by the extension 138) in the contact area 139 of the skin 99. Thus, the actual needle penetration depth 140 of the skin 99 is better characterized and controlled.

[0110] As shown in FIG. 60, the vial access member 21 of the transfer device 3 may include a plurality of lumens, such as a multi-lumen tube 34, to communicate with the fluid flow path 35 inside the transfer device 3. The vial access member 21 preferably includes one inlet tube 36 through which air or fluid enters the vial 12 and one outlet tube 37 through which air or fluid exits the vial 12. As shown in FIG. 59, for example, when the vial is inverted, the lumen opening 38 of the vial access member 21 can be oriented such that the opening of the inlet tube 36 is above the opening of the outlet tube 37. This orientation allows air or liquid to be introduced into the vial through the upper inlet tube 36 and exit the vial through the lower outlet tube 37. Further, the opening of the outlet tube 37 can be located adjacent to the partition 19 near the lower end of the inverted vial 12 such that all of the contents 14 of the vial 12 enter the outlet tube 37 and are removed from the vial 12. When the vial 12 is mounted in the vial holder docking region 29 of the transfer device 3, the vial access member 21 can access the contents 14 of the vial 12. When the transfer device 3 draws the contents 14 from the vial 12 to the outlet tube 37, a pressure drop 154 occurs in the vial 12. This pressure drop 154 causes air (displacement air) 58 to be drawn into the vial 12 through the opening of the inlet tube 36 of the vial access member 21 to replace the contents 14 being drawn in. In some cases depending on the amount of the contents 14 of the vial 12, the liquid level 153 of the vial 12 may be above the vial access member 21 and specifically above the opening of the inlet tube 36. When air 58 is drawn into the vial 12 through the opening of the inlet tube 36, it creates bubbles 155 in the contents 14. Buoyancy causes the bubbles 155 to move to the top of the vial 12 along with the existing air 58. In some contents 14, it is not preferred to introduce bubbles (air bubbles) 155 into the solution. This causes more foaming and causes foaming, frothing, and effervescence within the contents 14.

[0111] As shown in FIG. 61, the expandable member 156 can be slidably moved within the opening of the inlet tube 36 of the vial access member 21. The outer diameter of the expandable member 156 can be in close contact with the inner diameter of the opening of the inlet tube 36. The expandable member 156 can have an inner diameter through which air 58 passes. When air 58 is drawn into the vial 12 through the opening of the inlet tube 36 due to the pressure drop 154 in the vial 12, the air 58 first pushes the expandable member 156 like a piston within the opening of the inlet tube 36. The expandable member 156 is long enough not to protrude out of the opening of the inlet tube 36. The expandable member 156 continues to slide through the opening of the inlet tube 36 until the end of the expandable member 156 rises above the liquid level 153 within the vial and stops at the top 157 of the vial 12. The reversed cap of the vial 12 serves to stop the expandable member 156. The tip of the expansion step 156 can be tapered so as not to block the flow through the inner diameter when it contacts the top of the reversed vial 12. The air 58 continues to move through the inner diameter of the expandable member 156 until all of the contents 14 in the vial 12 are removed from the vial 12 to the outlet tube 37. As described above, the outer diameter of the expandable member 156 is in close contact with the inner diameter of the opening of the inlet tube 36 and does not leak air at this contact surface. The expandable member 156 ensures that no air 58 enters the vial 12 to cause bubbles (air bubbles) 155.

[0112] As shown in FIG. 62, the pressure chamber 59 can be configured with an inlet port 168 that brings the contents 14 and air 58 into the chamber. Further, the pressure chamber 59 can be configured to have an outlet port 64 for ejecting the contents 14 and air 58 from the pressure chamber 59. These ports 168, 64 can be arranged offset from the center of the pressure chamber 59 to assist in controlling the flow of the contents 14 and air 58 introduced into and / or discharged from the pressure chamber 59. As described above, the outlet port 64 of the pressure chamber 59 is disposed below the inlet port, and during the discharge of the contents 14 from the pressure chamber 59, first all of the contents 14 are discharged, and then the remaining air 58 is discharged last. All of the air within the pressure chamber 59 is directed upward toward the top of the pressure chamber 59. Further, as shown in FIG. 62, the outer shape of the outlet port can be a non-circular shape in order to cause all of the liquid contents 14 within the pressure chamber 59 to exit to the outlet port 64 and be removed from the pressure chamber 59 before removing the air from the pressure chamber 59. Further, as shown in FIG. 62, a portion 170 of the outlet port 64 can be placed below the surface 171 of the pressure chamber 59. This can act as a trap to further cause all of the liquid contents to enter from the pressure chamber 59 to the outlet port 64 and be removed from the pressure chamber 59 prior to the removal of the air 58 from the pressure chamber 59.

[0113] As shown in FIG. 63, when the contents 14 are removed from the vial 12 using the vial access member 21, only the contents 14 are removed through the opening of the outlet tube 37 until the liquid level 153 drops below the top of the opening of the outlet tube 37. At this time, a mixture of the contents 14 and air 58 is removed. As shown in FIG. 63, the vial access member 21 can further have an opening of the outlet tube 37 configured in a non-circular shape to reduce the height of the opening and increase the width of the opening to allow more of the liquid contents 14 of the vial 12 to enter the outlet tube 37 and be removed before removing the air from the vial 12.

[0114] As shown in FIGS. 64 and 65, the combination of the hydrophobic filter 68 and the hydrophilic filter 69 in the fluid flow path 35 between the vial 15 and the injection device 7 can preferably filter the contents 14 and remove the air 58 during the transfer process. This filter may be a separate element or may be combined into one element. Each filter may be composed of different materials including, but not limited to, mixed cellulose ester (MCE), polyvinylidene difluoride (PVDF), polytetrafluoroethylene (PTFE), nylon, and polyethersulfone (PES). Each filter may have a pore size in the range of 0.22 to 3 μm. Each filter is coated to be hydrophobic or hydrophilic.

[0115] When making an injection that is supposed to be subcutaneous, a common reaction is swelling of the injection area. This reaction is particularly noted in subcutaneous locations where the injection volume is high and / or the injection rate is fast. If the injection is being made with a syringe, needle, and administration set, the swelling of the injection area does not affect the injection device in any way. However, more drug is being used in automatic injection devices that are attached to the body during injection, and the swelling of the area presents difficulties in keeping the automatic injection device securely on the body. In particular, if the adhesive of the injection device is not properly designed, the lump or bulge formed by the solution injected onto the skin surface may cause the automatic injection device to be removed from the injection area. Therefore, there is a need for an automatic injection device with an appropriately designed adhesive that allows swelling in the injection area without jeopardizing the adhesion of the device to the patient.

[0116] As shown in FIG. 66, there are two interfaces with respect to adhering the injection device 7 to the skin 99. The first is the adhesive / device interface 173 and the second is the adhesive / skin interface 174.

[0117] As shown in FIG. 67, the adhesive 88 can be configured in the injection device 7 to have at least two regions. The first region 175 can include a permanent adhesive that uses mechanical or scientific means between the adhesive 88 and the injection device 7, and can preferably be disposed within the periphery of the injection device 7. The second region 176 can be configured such that it can be peeled or removed from the injection device 7, and can preferably be adjacent to the outside of region 1 (e.g., radially outward).

[0118] As shown in FIG. 68, if the adhesive 88 is fully attached to the lower surface (bottom) 76 of the injection device 7, since this adhesive / skin interface 174 is weaker than the adhesive / device interface 173, during the swelling 177 of the tissue, the adhesive at the adhesive / skin interface 174 will begin to peel away from the skin 99. This is shown in the bulging surface shown in FIG. 68. This will cause the injection device 7 to peel away from the surface of the skin 99 and fall off the patient.

[0119] As shown in FIGS. 67 and 69, instead of attaching the adhesive 88 completely permanently to the lower surface (bottom) 76 of the injection device 7 as shown in FIG. 68, the adhesive 88 can be configured in the above-described regions 175, 176 of the injection device 7. In this configuration, during the occurrence of the tissue swelling 177, the adhesive 88 in the second region 176 peels away from the injection device 7 and firmly adheres to the skin 99 at the adhesive / skin interface 174. This causes the transfer of the skin end portion 178 from the adhesive / skin interface 174 to the adhesive / device interface 173, and effectively relieves the distortion at the adhesive / skin interface. The adhesive / device interface 173 can be designed to be stronger to prevent the injection device 7 from separating from the surface of the skin 99.

[0120] When self - injecting using an auto - injection device, protecting the user from needle - stick accidents is a beneficial requirement for the device. Generally, the needle is stored within the device's confines before and after use, preventing the user from accessing it. However, during injection, the needle extends outside the device. While wearing the auto - injection device, if the user accidentally falls during injection, the needle poses a risk of needle - stick danger to the user. Therefore, there is a need for an auto - injection device to have a skin - removal sensor that automatically retracts the needle if the device becomes detached from the skin during injection.

[0121] As shown in FIGS. 70 - 72, the skin - removal sensor 179 is operably engaged with the flexible latch 181 of the button 77 and is slidable within the lower housing 180 of the injection device 7. As shown in FIG. 71, when the injection device 7 is attached to the surface of the skin 99, the skin - removal sensor 179 is forced to be in the first or upper position 182 of the injection device 7. When the button 77 is actuated (with the needle 85 exposed) to the injection state or the second position or the administration position, the flexible latch 181 is forced by the skin - removal sensor 179 to be in the locked position 187 below the latch plate 183. The latch plate 183 holds the button 77 on the latch - plate surface 84 in the injection state or in the administration position until the administration is complete. At the end of the administration, the latch plate 183 is released from the latch - plate surface 184 on the button 77, and the button 77 and the needle 85 are retracted to the post - injection position, and the needle is housed within the injection device 7. As shown in FIG. 72, if the injection device 7 is removed from the surface of the skin 99 during injection, the skin - removal sensor 179 extends to the second or lower position 185 outside the injection device 7. This causes the flexible latch 181 to spring back to the unlocked position and disengage from the latch plate 183. This also retracts the button 77 and the needle 85 to the post - firing position, and the needle 85 is housed within the injection device 7.

[0122] When performing self-injection with a syringe and needle, the user may need to temporarily stop or interrupt the injection due to severe pain or irritation in the injection area. This interruption of the flow of injectable medication into the injection area is achieved by removing the pressure on the plunger rod of the syringe, allowing a larger dose of the injectable fluid medication to be administered, allowing more time for it to diffuse into the surrounding tissue, reducing local pressure, and thereby reducing the associated pain and inflammation. However, more medication is being delivered by automated injection devices and the user is unable to manually interrupt this type of automated system. Once the automated injection device is placed on the skin and the cannula is once removed, there is no way for the user to pause the injection due to pain or irritation in the injection area. Accordingly, there is a need for the user to be able to pause the automated injection system.

[0123] As shown in FIGS. 73-74, simultaneously with the actuation of button 77, needle 85 and button 77 move to a first position or depth as shown in FIG. 73. At this first position or depth, the lateral hole 108 is covered by the partition wall 109. Accordingly, the lumen 165 of needle 85 is not in communication with the fluid channel 86 of the dosing port 82. Button 77 is intentionally held in the first position or depth to prevent the injectable contents 14 from flowing through the fluid channel 86, through the lateral hole 108 of needle 85, and into the skin 99. As shown in FIG. 74, when button 77 is released, needle 85 and button 77 return to a second position or dosing position, the lateral hole 108 is exposed to the fluid channel 86, and the injectable contents 14 flow from the fluid channel 86, through the lateral hole 108 of needle 85, and into the skin 99 until the end of the injection. This act of pushing button 77 to the first position or depth can be performed the necessary number of times throughout the injection.

[0124] As shown in FIGS. 75 to 76, the force (actuating force, load) 186 of the button 77 is the transition of the load applied to the button 77 that requires the displacement to start from the pre-injection position of the button 77 and the needle 85 to the injection state or the administration position. Until this transition load is applied, the force 186 to the button 77 is directly transferred to the injection device 7. In particular, this force 186 can be transferred to the adhesive / skin interface 174 and / or the adhesive / device interface 173, resulting in better certainty of the injection device 7 on the surface of the skin 99 before operating the injection device 7.

[0125] As shown in FIG. 77, the indication window 172 of the transfer instrument 3 may be present to indicate that the transfer and / or mixing of the content 14 is in progress. The indication window 172 may be configured in the base of the transfer instrument 3 and may track the movement of the plunger 93 in the pressure chamber 56 within the transfer device 3. The indication window 172 may be configured in a scale or other way to track the movement of the plunger 93. Alternatively, the plunger 93 may be configured in different colors to facilitate tracking its movement within the indication window 172. The combination of the indication window 172 and the plunger 93 may provide the progress of the drawing-in of the content 14 from the vial 12 and the filling of the pressure chamber 56. The combination of the indication window 172 and the plunger 93 may also provide the progress of the transfer of the content 14 from the pressure chamber 56 to the injection device 7.

[0126] As shown in FIGS. 78 - 79, the arcuate expandable member 78 is arranged in an arcuate shape in terms of length and / or is preferably extended. In the illustrated embodiment, the arcuate shape is induced by providing a region of reduced strength, such as a thick region 126 of a thicker or heavier wall. In that region, the expandable member will warp less and form an expanded arcuate shape. The thick region 126 of the heavy wall can be configured in any shape that causes the expandable member 78 to assume an arcuate shape during inflation. A more preferred structure of the thick region 126 of the heavy wall is to minimize its thickness or the circumferential fixtures 150 on the wall of the expandable member 78, and to minimize the radial thickness or the protrusions 151 away from the expandable member 78. This helps to encourage the expandable member 78 to expand in an arcuate shape, while minimizing the amount of surrounding material that is not affected by the thick region 126 of the heavy wall for inflation. Although not limiting, a T - shaped configuration can be formed at the ends of the radial protrusions 152 to assist the expandable member 78 in expanding in an arcuate shape.

[0127] As shown in FIG. 80, the volume of the pressure chamber 56 can be set to be larger than the total volume of the fluid in the vial 15 so that additional air 58 can be drawn into the pressure chamber 56 from the vial 15. This additional air can be useful to ensure that all of the contents 14 are removed from the vial 15 and to check for the removal and cleaning of the remaining contents 14 in the fluid flow path 35 between the vial 15 and the pressure chamber 56. Further, additional air may be useful for the removal or cleaning of any remaining contents 14 in the fluid flow path 35 between the pressure chamber 56 and the injection device 7 during the transfer of the contents 14 from the pressure chamber 56 to the injection device 7.

[0128] As shown in FIG. 81, the transfer device 3 includes a vial holder docking area 29 that may include an elongated vial access member 21. The vial holder docking area 29 may include a vial access protection portion 136. The vial access protection portion 136 is locked and held by a locking finger 137 at a first position above the vial access member 21 in the vial holder docking area 29 to cover the vial access member 21 and prevent the vial access member from accidentally stabbing the user prior to the insertion of the vial 12 or the vial holder. When the vial 12 or the vial holder is inserted into the vial holder docking area 29, the vial 12 or the vial holder displaces the locking finger 137 to release the lock of the vial access protection portion 136. When the lock is released, the vial access protection portion 136 is capable of sliding and moving together with the vial 12 or the vial holder within the vial holder docking area 29.

[0129] As shown in Fig. 82, the flow restrictor 55 can be used to control and / or delay the transfer time and / or increase the mixing time within the fluid flow path 35. A small lumen tube can be used to restrict the flow at any point in the fluid flow path 35 and increase the mixing / transfer time to more than one hour. One way to control and / or cause a transfer time delay and / or increase the mixing time between the second pressure chamber 42 and the injection device 7 is to use a multi-lumen fluid flow path 142 between the second pressure chamber 42 and the injection device 7. Each lumen 143, 144 of the fluid flow path 142 is preferably spaced by the movement distance of the piston at the second pressure chamber 42, and the inner diameters 147, 148 are sized to provide a specific flow rate through the lumens 143, 144 based on the pressure within the second pressure chamber 42 and are attached at specific positions 145, 146. Initially, when the piston 46 of the second pressure chamber starts to advance within the second pressure chamber 42, the fluid contents 14 are administered through all the lumens 143, 144 into the fluid flow path 142 towards the injection device 7. When the piston passes through the attachment point 145 between the lumen 143 and the second pressure chamber 42, the flow of fluid through that lumen 143 stops and the contents 14 are forced to flow through the remaining lumen 144. The multiple lumens and attachment points can be arranged along the pressure chamber. The final lumen 144 available from the flow of the contents 14 will have a very small inner diameter. Thus, the flow rate will be very slow and the time to transfer the contents 14 from the second pressure chamber 42 to the injection device 7 will increase. This transfer delay increases the mixing time.

[0130] As shown in Fig. 83, a safety mechanism (safety device) 100 such as a safety pin or a safety sleeve can be configured to be removed from the injection device 7 in any direction of release to release the injection device 7 for injection preparation.

[0131] As shown in FIG. 84, when the button 77 of the injection device 7 is fully pressed, the injection device 7 includes a needle 85 having a lateral hole 108 that enables fluid communication between the fluid channel 86 and the skin 99. This initiation administers the injectable contents 14. The lumen 165 of the needle 85 is important in controlling the rate of administration from the injection device 7. Referring to the Hagen - Poiseuille equation for fluid flow in a tube, the flow rate through the tube is proportional to the fourth power of the radius of the tube. Thus, especially when the lumen 165 is small, changing the inner diameter of the needle 85 slightly can greatly change the flow through the needle 85. The needle 85 within the injection device 7 can be in the range of 21G to 34G (Stubs Iron Wire Gauge System) at various wall thicknesses. This range corresponds to an inner diameter of the lumen 165 of the needle from 0.021” to 0.003” with manufacturing variations and tolerances for any given needle size. This is based on the needle size and the inner diameter has a variation of about ±0.00075”. The needle 85 can be modified before being assembled into the injection device 7 to limit the range of the inner diameter of the lumen 165 and thus limit the variation in flow. This modification can include folding, flattening, or rolling the needle over more than a portion of its length to a new defined effective inner diameter of the lumen 165, from circular to non - circular. This has the advantage of enabling control of a specific delivery rate from the injection device 7.

[0132] As shown in FIGS. 85-86, the lumen opening 38 of the vial access member 21 can be directed to introduce pressurized air or liquid through the upper inlet tube 36 and output the contents 14 of the vial through the lower outlet tube 37. Further, the opening of the outlet tube 37 can be disposed adjacent to the partition wall 19 near the bottom of the inverted vial 12 such that all of the contents 14 of the vial 12 enter the outlet tube 37 and are removed from the vial 12. The preferred order of removal of the contents 14 from the vial 12 is first all of the contents 14 in the vial 12 and then air 58 from the vial 12. This is achieved in the current embodiment when the direction of the transfer device 3 is directed as shown in FIGS. 85-86. Based on the shape of the vial access member 21 within the vial 12, this order of removal of all of the contents 23 and then air 58 is achieved with the angle of the transfer device 3 from horizontal up to ±45°. Beyond this angle, it causes air 58 to be introduced during the removal of the contents 14 from the vial 12. A sensor (angle sensor) 149 is disposed within or around the vial access member 21 to sense the angle of the transfer device 3. Each or any of the lumen openings 38 and / or can have a direct communication directly between each or any of the inlet tube 36 and the outlet tube 37. In the current embodiment shown in FIG. 85, when the transfer device 3 is at an angle less than 45°, the sensor 149 fluidly communicates between the outlet tube 37 and the fluid flow path 35. As shown in FIG. 86, if the transfer device 3 is tilted more than 45°, the sensor 149 rotates or moves to a new position to block the fluid communication between the outlet tube 37 and the fluid flow path 35.

[0133] As shown in FIG. 87, another transfer device 3 within a single vial system is provided that does not perform mixing but transfers the contents 14 from a single vial 12 to the injection device 7. This other transfer device 3 includes the vial 12, a variable volume pressure chamber 56, and a fluid flow path 35 for directing the contents 14 from the vial 12 to the injection device 7. The inlet tube 36 of the vial access member 21 is connected to a variable volume pressure chamber 56 having a fluid flow path 35. The outlet tube 37 of the vial access member 21 is connected to the injection device 7 through the pressure chamber 56 of the fluid flow path.

[0134] As shown in FIG. 87, the complete insertion of the vial 12 into the transfer device 3 by the user causes the introduction of the vial access member 21 through the partition wall 19 of the vial 12 to access the contents 14 of the vial 12. This also induces the release of the trigger 49 of the pressure chamber. The plunger 60 in the retracted position and the pressure chamber 56 are filled with air 135. The trigger 49 releases the plunger 60 within the pressure chamber 56 that is connected to the dosing spring 63. The dosing spring 63 advances the plunger 60 and replaces the air 135 from the pressure chamber 56 into a single vial 12 through the inlet tube 36. The air 135 entering the vial 12 replaces the contents 14 through the outlet tube 37 and into the injection device 7 outside the vial 12. This continues until all of the contents 14 are replaced out of the vial 12 and into the injection device 7. The check valve 40 can be used to prevent the contents 14 from returning to the vial 12 or to prevent the contents 14 from returning to the pressure chamber 56.

[0135] The subject matter has been described with respect to specific examples for purposes of illustration only and not for purposes of limitation. The scope of the subject matter is not limited to the illustrated embodiments or their equivalents alone, but is to be understood to have a broader application in modified configurations and uses that are some of which are obvious upon reading this description and others and others which are obvious after some study and / or development.

Claims

1. An apparatus for filtering a liquid drug, comprising: a. a housing including an injectable fluid passageway; and b. a liquid drug filter disposed within the injectable fluid passageway and having a liquid drug pore size or liquid drug effective pore size configured to remove particulate matter; further comprising a liquid drug transfer device, wherein the housing includes a vial receiving portion and a liquid outlet port, and the injectable fluid passageway includes an injectable fluid passageway inlet configured to receive a liquid drug from a vial disposed in the vial receiving portion and an injectable fluid outlet in fluid communication with the liquid outlet port.

2. The transfer device is configured to reconstitute a lyophilized drug as the liquid drug, and the liquid drug pore size or the liquid drug effective pore size is configured to remove undissolved lyophilized drug. The apparatus according to claim 1.

3. The housing of the transfer device further includes a displacement air passage having a displacement air passage inlet in fluid communication with a source of displacement air and a displacement air passage outlet configured to direct displacement air to the vial, and further comprises a displacement air filter having a pore size small enough to prevent pathogens from being introduced into the vial. The apparatus according to claim 1.

4. The displacement air filter has a pore size or effective pore size of about 0.22 μm or less. The apparatus according to claim 3.

5. The displacement air filter is a membrane. The apparatus according to claim 3.

6. The displacement air filter is a depth filter. The apparatus according to claim 3.

7. The displacement air passage inlet is a vent hole, and the source of displacement air is the atmosphere. The apparatus according to claim 3.

8. The source of displacement air is pressurized to a predetermined pressure, the liquid drug filter is a hydrophilic filter, further comprising a hydrophobic filter and a vent filter housing, the vent filter housing is disposed in the injectable fluid passageway and houses the hydrophobic filter and the hydrophilic filter of the liquid drug, the hydrophobic filter is in fluid communication with the vent hole, the hydrophilic filter of the liquid drug is in fluid communication with the liquid outlet port, and the hydrophilic filter of the liquid drug has a pore size or effective pore size based at least in part on a predetermined pressure such that displacement air does not pass through the liquid outlet port. The apparatus according to claim 3.

9. An apparatus for filtering liquid medicine, comprising: a. A housing including an injectable fluid passageway; b. A liquid medicine filter disposed within the injectable fluid passageway and having a liquid medicine pore size or a liquid medicine effective pore size configured to remove particulate matter; and further comprising: A liquid medicine transfer device; The housing includes a skin-facing surface including a needle opening through which a needle extends from the housing; The needle has a needle lumen in fluid communication with an outlet of the injectable fluid passageway. An apparatus. **Claim 10** The apparatus according to claim 9, further comprising an arcuately expandable elastic bag configured to hold a volume of liquid medicine within the housing, the arcuately expandable elastic bag being in fluid communication with an inlet of the injectable fluid passageway.

Images