Systems and methods for drug delivery device reconfiguration

Abstract

A drug reconstitution system and related methods are disclosed herein. The drug reconstitution system may include a first component in a first container in a storage state and a second component in a second container in a storage state. The first component may be selected from the group of a drug product, a diluent, saline, and an intravenous stabilization solution ("IVSS"). The second component may be selected from the group of a drug product, a diluent, saline, and an IVSS. The first component may be different from the second component. At least one fluid pathway may be configured to at least selectively fluidly connect the first container and the second container. A biasing assembly may be configured to selectively bias at least a portion of the first component from the first container into contact with the second component.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority to U.S. Provisional Application No. 62 / 923,040, filed October 18, 2019, entitled "Systems And Approaches For Drug Delivery Device Reconstitution", the entire contents of which are hereby incorporated by reference.

[0002] The present disclosure generally relates to drug delivery devices, and more particularly to reconstitution techniques for drug delivery devices.

Background Art

[0003] Drugs are administered to treat various conditions and diseases. Intravenous (IV) therapy is a drug administration process that delivers drugs directly into a patient's vein using a drip solution contained within a delivery container (e.g., a soft bag). These drug administrations may be performed in a medical facility or, in some cases, at a remote location such as the patient's home. For certain applications, drug products may be shipped in powder or lyophilized form to medical facilities (e.g., inpatient facilities, outpatient facilities, and / or pharmacies).

[0004] When reconstituting these drugs for administration, it is particularly important to maintain a sterile environment so as not to deteriorate or otherwise compromise the quality of the drug. Additionally, some classes of drugs, such as bispecific T cell engagers, may require extremely precise amounts of drug product and / or other fluids required for administration to prevent the drug product from becoming toxic. Often, medical professionals must prepare drugs by strictly following a set of steps to ensure that a sterile environment is maintained and that the correct amounts of ingredients are added to the delivery container. When reconstituting these drugs for administration, it may be desirable or necessary to utilize a diluent, such as by adding the diluent to the drug product vial. As a result of these various steps and requirements, the reconstitution process can be time-consuming and tedious, and can result in unacceptable or undesirable error rates.

[0005] The current process for reconstituting lyophilized oncology products is often performed by licensed pharmacists in either hospital or specialty compounding pharmacies. The use of a hood is often required to perform the reconstitution process, which provides a sterile working environment that can be cumbersome for pharmacists given the complexity of the process. Additionally, this reconstitution process involves the use of multiple needles to withdraw / add sterile water for injection (WFI), saline, and / or intravenous solution stabilizer (IVSS) solutions. Typically, for relatively complex oncology products, such as bispecific T-cell engager (BiTE®) molecules (e.g., Blincyto®) prepared in IV bags, a specific amount of WFI is added to reconstitute the lyophilized drug product contained in a vial using a needle and syringe system. Then, appropriate amounts of saline and IVSS solutions are added to the empty IV bag before the reconstituted final drug product is introduced. The entire process can require up to five needle and syringe systems, each involving manual handling time and potential needle exposure. Furthermore, the use of a hood during this complex preparation can pose risks.

[0006] Additionally, due to current regulatory requirements implemented by the National Institute for Occupational Safety and Health (NIOSH), certain oncology products are on the hazardous drug list, which requires the use of additional engineering controls, such as closed system drug delivery systems (CSTDs), as an added safeguard. Also, regardless of whether a drug is on the NIOSH list, it may be advantageous to utilize CSTDs and / or other components / systems to minimize or prevent unwanted release of fumes into the air or other exposures.

[0007] As described in further detail below, the present disclosure describes systems and methods for reconfiguring drug delivery devices that embody advantageous alternatives to existing systems and methods, and that may address one or more of the problems or needs described herein as well as provide other benefits and advantages. Summary of the Invention [Means for solving the problem]

[0008] An embodiment of the present disclosure provides a drug reconstitution system including a first component, a second component, at least one fluid pathway, and a biasing assembly. The first component may be selected from the group consisting of a drug product, a diluent, saline, and an intravenous stabilization solution ("IVSS"). The first component is in a first container in a storage state. The second component may be selected from the group consisting of a drug product, a diluent, saline, and an IVSS. The first component may be different from the second component, and the second component may be in a second container in a storage state. The at least one fluid pathway may be configured to at least selectively fluidly connect the first container and the second container. The biasing assembly may be configured to selectively bias at least a portion of the first component from the first container into contact with the second component.

[0009] A further aspect of the present disclosure provides a method of preparing a drug for delivery. The method includes (a) providing a diluent contained within a diluent container, (b) providing a drug product contained within a drug product container, (c) providing a fluid path system that physically connects the diluent container and the drug product container, the fluid path system having a storage configuration in which the diluent container and the drug product container are not in fluid communication with each other and a first mixing configuration in which the diluent container and the drug product container are in fluid communication with each other, and (d) adjusting the fluid path system from the storage configuration to the first mixing configuration to urge at least a portion of the diluent from the diluent container and / or at least a portion of the drug product from the drug product container to form a drug product / diluent mixture.

[0010] The above need is at least partially satisfied through the provision of systems and techniques for drug delivery device reconstitution as described in the following detailed description, which is to be studied in particular in conjunction with the drawings.

Brief Description of the Drawings

[0011] [Figure 1] Exemplary drug reconstitution systems according to various embodiments are shown. [Diagram 2] Exemplary drug reconstitution systems according to various embodiments are shown. [Diagram 3] Exemplary control components according to various embodiments are shown. [Figure 4] Exemplary drug reconstitution methods according to various embodiments are shown.

Modes for Carrying Out the Invention

[0012] Those skilled in the art will understand that the elements in the figures are drawn for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to aid in understanding the various embodiments of the present invention. Also, elements that are common but well understood and useful or necessary in a commercially viable embodiment are often not shown so as not to unduly obscure the figures of these various embodiments. Further, it will be recognized that certain acts and / or steps may be described or shown in a particular order of occurrence, but those skilled in the art will understand that such particularity with respect to the order is not actually necessary. As used herein, the terms and expressions have the ordinary technical meaning as would be given by those skilled in the art, as described above, unless a different specific meaning is set forth herein.

[0013] The present disclosure relates to a closed drug preparation system that provides a sterile environment that can achieve an improved preparation environment, thereby reducing the risk of preparation and the number of preparation steps. As a more specific example, the present disclosure relates to systems and methods that can provide the advantages and / or precautions of a closed drug transfer system (CSTD), but provide a disposable, portable, and easy-to-use system or method.

[0014] As a more specific example, a drug reconstitution system and method are described herein, and the drug reconstitution system and method generally include a first component selected from the group consisting of a drug product, a diluent, a saline solution, and an intravenous stabilization solution ("IVSS"), the first component being in a first container in a storage state, a second component selected from the group consisting of a drug product, a diluent, a saline solution, and an IVSS, the first component being different from the second component, and the second component being in a second container in a storage state, at least one fluid path configured to at least selectively fluidly connect the first container and the second container, and a biasing assembly configured to selectively bias at least a portion of the first component from the first container into contact with the second component.

[0015] The biasing assembly may include, hereinafter, a pump at least selectively coupled to at least one fluid path, at least one fluid path valve, at least one fluid path clamp, at least one fluid path closure component, at least one gravity flow differential, an inclined plane, a raised container support, or one or more of a load cell.

[0016] The drug reconstitution system may include a third component selected from the group consisting of a drug product, a diluent, a saline solution, and an IVSS, the third component being different from the first and second components. The third component is in a third container in a storage state. The first, second, and third containers may be packaged as a common kit package.

[0017] The drug reconstitution system may include a fourth component selected from the group consisting of a drug product, a diluent, a saline solution, and an IVSS, the fourth component being different from the first, second, and third components. The fourth component is in a fourth container in a storage state. The first, second, third, and fourth containers may be packaged as a common kit package.

[0018] A drug reconstitution method may generally include providing a fluid pathway system physically connecting a diluent container and a drug product container, the fluid pathway system having a storage configuration in which the diluent container and the drug product container are not in fluid communication with each other and a first mixing configuration in which the diluent container and the drug product container are in fluid communication with each other, and adjusting the fluid pathway system from the storage configuration to the first mixing configuration to force at least a portion of the diluent from the diluent container and / or at least a portion of the drug product from the drug product container to form a drug product / diluent mixture.

[0019] The drug reconstitution method may also include adjusting the fluid pathway system to a second mixing configuration to force at least a portion of the saline from the saline container and / or at least a portion of the IVSS from the IVSS container to form a saline / IVSS mixture.

[0020] As another example, a sterile, disposable tubing manifold and other components may be utilized to reconstitute lyophilized drug products for use at the point of care. As a more specific example, the disposable tubing manifold and other components facilitate all of the steps necessary to perform the reconstitution process, providing a "closed" process that potentially eliminates the need for a hood and the safety risks associated with using multiple needles to reconstitute drug products, such as oncology drugs. Additionally, the system may have integrated automation features that allow patients to perform the reconstitution themselves in preparation for self-administration of the drug in the patient's delivery device.

[0021] The system may include a sterile single-use tubing system, and the valve system is used to reconstitute the lyophilized compound into the final IV bag that the patient is to receive. This system can be made essentially modular with solutions for different sizes / volumes integrated. In one use, the tubing manifold is manual and is used by a pharmacist or healthcare provider appropriately trained to adjust similar drug dosages. In another use, the system is automated to be even more user-friendly and / or allow the patient to perform the reconstitution themselves.

[0022] Referring to FIG. 1, in accordance with these various embodiments, a drug delivery system 100 or kit and a corresponding method of preparing a drug delivery device using the drug delivery system 100 are provided. A medical professional, caregiver, or patient can use the drug delivery system 100 to prepare a drug delivery device for delivery to a patient. The drug delivery system 100 differs from conventional systems in that many of the components contained within the system 100 are pre-filled and / or pre-mixed at the correct dosage. As a result, while ensuring that the correct amount of components are administered, it reduces the preparation of the drug delivery device by a medical professional, caregiver, or patient. The system 100 may be used to provide intravenous, subcutaneous, intra-arterial, intramuscular, and / or epidural delivery techniques. By using this system 100, a patient's anxiety and / or confusion may be reduced due to a reduction in the complexity and waiting time of the preparation caused by the drug preparation process. Additionally, the system 100 may allow a healthcare provider, pharmacist, patient, and / or other individuals involved in the preparation, provision, or use of the drug to have a more rationalized, predictable, and / or effective process for drug delivery. For example, the system 100 may reduce the time it takes for a pharmacist to prepare a drug used by a patient, reduce the number of steps that must be performed manually by a pharmacist to prepare a drug used by a patient, and / or improve the overall efficiency of the drug preparation process. As a more specific example, the system 100 may be particularly advantageous for use in drug preparation involving several steps, such as adding a diluent and then adding a solution containing saline and / or IVSS, and / or drug administration that requires a long preparation time.

[0023] The drug delivery system 100 shown in FIG. 1 generally includes a drug product container 110 that houses a drug product 112, a diluent container 120 that houses a diluent 122, a saline container 130 that houses saline 132, an intravenous stabilization solution ("IVSS") container 140 that houses IVSS 142, and a fluid path assembly 160 configured to selectively, fluidly couple or disconnect the various aforementioned components.

[0024] For example, the fluid pathway assembly 160 may include a tubing manifold 162 having a series of connection points for physically connecting the respective containers 110, 120, 130, and 140 to one another. As a more specific example, the connection points may include quick-connect sterile connectors with respective subcomponents that selectively mate with one another while maintaining sterility or another desired standard of cleanliness. For example, the quick-connect sterile connectors may snap, interlock, or thread together; the quick-connect sterile connectors may have sheathed and sheathed components that are unsheathed or uncovered upon connection; and / or the quick-connect sterile connectors may have a luer lock or modified luer lock configuration. As another example, the connectors may include one or more stake connectors for coupling one of the tubing 162 sections with an IV bag.

[0025] Moving on to FIG. 1, for example, adapter 164 may be a closed drug transfer system (“CSTD”) that fits snugly onto drug product container 110, which may be a vial, or a suitable vial adapter. Similarly, adapter 166 may be a vial adapter that fits snugly onto diluent container 120, which may also be a vial. Similarly, adapter 168 may be a vial adapter that fits snugly onto IVSS container 140, which may be a vial. Any or all of containers 110, 120, 140 may be vials with standard septa that are pierced by vial adapters or vial stakes, and additionally or alternatively, any or all of containers 110, 120, 140 may include quick-connect sterile connectors or other suitable connectors. Alternatively, any or all of containers 110, 120, 140 may be flexible containers such as IV bags or any other suitable container. Each of containers 110, 120, 140 is shown in an upright configuration in FIG. 1, but may be connected to fluid path assembly 160 by allowing the container to be inverted so that the contents flow out by gravity. However, if drug product 112 or other components are in solid form, it may be beneficial or desirable to force fluid into the vial to reconstitute the solid components in order to facilitate and / or improve the discharge process.

[0026] Saline container 130 may be an IV bag, a vial, or any other suitable container. Saline container 130 is coupled to fluid path assembly 160 via one or more ports 170, 172, as shown in FIG. 1. For example, an IV spike (not shown) may pierce ports 170, 172 to physically connect saline container 130 to fluid path assembly 160. The IV bag shown in FIG. 1 is coupled to a hook 134 for hanging the bag to provide a gravity drainage function.

[0027] The system 100 shown in FIG. 1 also includes a final drug product bag 190 for collecting and storing the final mixture of the drug product, and this final mixture can be delivered to and / or stored for a patient. The system 100 also includes a waste bag 196 for receiving an excess amount of components and / or the final drug product. Although both of these components are shown in the system 100 of FIG. 1, the system 100 may operate without one or both of those containers, such as by storing the final mixture of the drug product within one of the other containers 110, 120, 130 and / or holding an excess amount of components and / or the final drug product within the container and / or within a length portion of the tube 162.

[0028] Each of the containers 110, 120, 130, and 140 shown in FIG. 1 is in a storage state in which the containers are not fluidly coupled to one another. Once each of the containers 110, 120, 130, and 140 shown in FIG. 1 is physically connected to the fluid path assembly 160 via the above or another suitable means, the containers 110, 120, 130, and 140 may still remain in a storage state and not be fluidly coupled to one another. For example, even once each of the containers 110, 120, 130, and 140 is fluidly coupled to a different portion of the fluid path assembly 160, the containers may be fluidly decoupled or isolated from one another by one or more fluid closure components, such as valves or clamps that facilitate or create closure. As a more specific example, FIG. 1 shows a series of valves that can fluidly isolate the containers from one another individually and / or collectively. Valve 124 is positioned adjacent to adapter 166 so that diluent 122 does not flow into fluid contact with any of the other containers 110, 130, 140, even when diluent container 120 is connected to adapter 166 and gravity is acting on diluent 122. As shown in FIG. 1 , valve 124 is positioned along a generally vertical portion of tube 162, although other configurations may be suitable. Valves 126 and 128 are each positioned along a generally horizontal portion of tube 162 on either side of the vertical portion, such that valve 126 controls access to the portion of fluid pathway assembly 160 leading to drug product container 110, and valve 128 controls access to the portion of fluid pathway assembly 160 leading to waste bag 196.

[0029] 1 may further include a valve 114 positioned along a vertical portion of the pipe 162 adjacent to the drug container 110, the valve 114 selectively restricting fluid communication with the drug container 110. Similarly, the system 100 includes a valve 116 positioned along a horizontal portion of the pipe 162 adjacent to the final drug product container 190, the valve 116 selectively restricting fluid communication with the container on the drug product / diluent side of the system 100.

[0030] The system 100 shown in FIG. 1 may also include a pair of valves 136, 138 positioned along the vertical portion of the tube 164 that supports the adapters 170, 172, thereby selectively restricting the fluid connection between the saline container 130 and other containers. The system 100 shown in FIG. 1 may further include a valve 144 positioned along the vertical portion of the tube 162 adjacent to the IVSS container 140 that selectively restricts the fluid connection to the IVSS container 140. Similarly, the system 100 includes a valve 146 positioned in the horizontal portion of the tube 162 adjacent to the final drug product container 190, the valve 146 selectively restricting the fluid connection between the saline / IVSS side containers of the system 100.

[0031] The fluid closure component utilized in the system may be any suitable component or feature that selectively permits or restricts the movement of fluid within the fluid path assembly 160. For example, if the fluid closure component is a valve, the fluid closure component may have an external handle that, when turned, opens or closes a ball joint portion housed within the fluid closure component. As a more specific example, the valve may be a one-way valve, a two-way valve, a three-way valve, or some other type of stop valve suitable for selectively stopping or restricting flow. As another example, the fluid closure component utilized in the system may be a clamp that constricts a local portion of the tube 162 to block or restrict the flow of fluid through the tube 162. Such a clamp is preferably a removable one, such as a throttle clamp, having a clamping force sufficient to completely or substantially occlude the desired portion of the tube 162. It may be advantageous to utilize a clamping clamp that can be moved from one location to the next in order to reduce the total number of system components. Additionally, the fluid closure component, such as a manual valve or clamp, may be manually operated, or may be automatically controlled, such as an electronic valve or flow restrictor controlled by a system controller or a central processing unit ("CPU") (shown in FIG. 2).

[0032] The fluid closure component described above can selectively restrict or block the flow through the fluid closure component, but the fluid closure component may also serve as a component of the biasing assembly, particularly when combined with other components. For example, a pump 180, a gravity flow differential (e.g., an inclined configuration shown by the inclined table 184), or a raised container support (e.g., hooks 134 and / or the vertical portions of the tubes supporting containers 110, 120, 140) may be configured to selectively bias the contents of one container toward and / or into fluid contact with the contents of another container.

[0033] The pump 180 shown in FIG. 1 is in a first position 182 along the fluid path between the diluent container 120 and the drug product container 110. The pump 180 may also be used at a second position 183 along the fluid path between the saline container 130 and the IVSS container 140. The system 100 may include a single pump movable between two positions, a single non-movable pump, two or more non-movable pumps, or another suitable configuration. In the case of a single pump, the system 100 may rely on gravity flow and / or a raised container support to selectively bias the contents of one container toward and / or into fluid contact with the contents of another container. The pump 180 shown in FIG. 1 is preferably a portable peristaltic pump, but other types of pumps may be used. Alternatively or additionally, a positive displacement pump may be more difficult to move from one location to another within the system 100, but such a pump may be used.

[0034] One objective of the system 100 shown in FIG. 1 may be to utilize a disposable tubing manifold design (fluid flow path assembly 160 and other containers, adapters, and valves) to incorporate all components required during a complex tumor treatment reconstitution process into a single manifold to reduce safety risks associated with needles and hazardous drugs. In this disposable tubing manifold design, tubing 162 may be manufactured, assembled, gamma-irradiated to be sterile, and ready to use. The tubing manifold, sterile quick connects, vial adapters, and CSTDs are integrated to provide the appropriate connections to each compound required during reconstitution. The tubing manifold design is intended to be flexible enough to allow for the addition of additional connections to accommodate the addition of other drug product (DP) compounds; The tubing manifold is modular in nature so different volumes of diluent, DP, and IVSS can be installed based on the application / use case. The final drug product bag may be flexible in volume in the case of weight-based dosing regimens; If a saline or WFI bag is used, the saline or WFI bag may be suspended in a gravity grain to exclude air; An optional waste bag may be added to the tubing manifold to provide necessary drainage; It should be noted that the length of each tubing segment and the placement of bags or vials along the tubing manifold can be modified based on the use case and to reduce the overall holding volume. The entire tubing manifold may be used in gradients to allow for optimal drainage and filling with minimal voids.

[0035] During one exemplary method of operating the system 100, the following steps may be utilized. Step 1: By isolating the desired fluid pathway, i.e., (a) closing valves 126 and 116; (b) opening valves 124, 128, 114; (c) adding diluent 122 to drug product container 110 by utilizing pump 180 in first position 182 to force diluent 122 into drug product container 110; Step 2: Isolate the mixture of diluent 122 and drug product 112 in the horizontal section of pipe 162 by closing valves 124 and 114 . Step 3: By isolating the fluid pathway and outlet of the saline bag, i.e. (a) closing valves 146 and 172; (b) opening valves 136 and 144; (c) adding IVSS 142 to saline container 130 by using pump 180 in second position 183 to force IVSS into saline container 130; Step 4: Transfer the mixture of saline 132 and IVSS 142 into the final drug product bag 190, i.e., (a) closing valves 136 and 144; (b) Valves 138 and 146 are opened to allow the IVSS / saline mixture to flow into the final drug product container 190 . In this step, it may be desirable or advantageous to operate pump 180 in second position 183 but in the opposite direction to step 3, i.e., to pump the mixture toward final drug product container 190. Step 5: Valve 146 is closed and valve 116 is opened, allowing the mixture of drug product 112 and diluent 122 to flow into final drug product container 190. At this step, it may be desirable or advantageous to operate pump 180 in first position 182 to pump the mixture toward final drug product container 190.

[0036] Note that the volume added / attached to the tubing manifold is calculated prior to performing the process. The final form of any of the solution containers may be either a vial, bag, or pre-filled syringe configuration.

[0037] In some scenarios, withdrawing liquid from any one of containers 110, 120, 130, and 140 may create a vacuum effect within the container, which may increase the suction force required to remove fluid from the container. To counteract this vacuum effect, some or all of containers 110, 120, 130, and 140 may incorporate at least one vent that allows air or another gas to fill the container as fluid is withdrawn from the container. Additionally, in some embodiments, system 100 may include one or more mechanisms for preventing gas drawn through the vent from being drawn into the fluid path after the container with which the vent is associated has been emptied. Such mechanisms may include, for example, a timer configured to turn off pump 180 after a certain amount of operation; a meter coupled to one or more of containers 110, 120, 130, and 140 to determine whether the container is empty; a hydrophilic filter coupled to the outlet of one or more of containers 110, 120, 130, and 140 configured to allow the passage of fluid but not gas; a trip switch coupled to pump 180 configured to turn off pump 180 when pump 180 is no longer drawing fluid; and / or other suitable means for preventing air from entering the fluid path.

[0038] 1 includes dimensions corresponding to the distances between various components of system 100. These dimensions are merely exemplary, and other dimensions are possible depending on various manufacturing, operational, and / or therapeutic considerations, including, for example, the size of the containers and / or other components included in system 100 and / or the volume of the reconstituted drug product to be produced.

[0039] The drug delivery system 200 shown in FIG. 2 generally includes a drug product container 210 containing a drug product 212, a diluent container 220 containing a diluent 222, a saline container 230 containing saline 232, an intravenous stabilization solution ("IVSS") container 240 containing an IVSS 242, and a fluid pathway assembly 260 configured to selectively fluidly couple or decouple the various aforementioned components.

[0040] System 200 shown in Figure 2 includes many components similar to or identical to those shown and described above in Figure 1. Elements of system 300 not further detailed herein may have a configuration, function, and / or structure similar to or identical to the correspondingly numbered elements described above with respect to system 100 shown in Figure 1.

[0041] One primary difference from system 100 of Figure 1 is that system 200 shown in Figure 2 includes at least two pumps 280, 285, each of which is preferably relatively fixedly connected to fluid path assembly 260, rather than being easily removable from system 100 like pump 180 of Figure 1. A third pump 287 may also be utilized. Pumps 280, 285, 287 may include disposable pump heads (peristaltic or positive displacement). Pumps 280, 285, 287 may be driven by permanently attached motors and shafts and are connected to a user interface and / or pump controller (as described in further detail below).

[0042] The additional pumps 285, 287 allow system 200 to be utilized or operated with fewer steps, such as disconnecting and reconnecting the pumps. Accordingly, system 200 may be suitable for use by individuals who have little time to prepare mixtures and / or little training or experience in preparing relatively complex drug mixtures. For example, system 200 may be suitable for use by a patient or healthcare provider in addition to a pharmacist. As a more specific example, system 200 shown in FIG. 2 may allow a patient to perform the reconstitution process independently, without the assistance of a pharmacist.

[0043] Another main difference is that the system 200 shown in FIG. 2 includes a controller 295 or a central processing unit (“CPU”) for controlling all or some of the components of the system 200. For example, the system 200 may be operable by pressing a button (or a series of buttons) or other commands. As another example, the system 200 may be coupled to an external computer and / or a smartphone for its control. Such functionality may require or utilize wireless communication components such as Bluetooth or WiFi technology. As another example, FIG. 3 shows an exemplary controller and / or interface 395 that enables a user to control the operation of the system 200.

[0044] Another main difference is that the system 200 shown in FIG. 2 includes at least one meter, such as a meter 297 for measuring the saline container 230 and a meter 299 for measuring the final drug product container 290. The system 200 may utilize fewer or additional meters, if desired. The meters 297, 299 shown in FIG. 2 may enable a user to monitor the progress of the mixing process. The meters 297, 299 shown in FIG. 2 may also, or alternatively, be coupled to the CPU 295 and / or the controller 395 such that the CPU and / or the controller 395 can use the data from the meters 297, 299 for the operation of the system 200. For example, the inputs from the meters 297, 299 may be utilized by the CPU 295 and / or the controller 395 to determine the progress of a particular process and / or to determine when to move to the next step in the process.

[0045] Additionally or alternatively, meters 297 and / or 299 can be connected to controller 395 to provide real-time monitoring of the addition / reconstitution process as a means of monitoring the volume of the solution. In this concept, the patient simply performs the process on a user interface, and the pumps / meters / valves are controlled by an electronic controller PCB module (not shown). For example, Figure 3 shows a series of buttons that can be notification indicators (e.g., lights) to notify the user of the status of the mixing process and / or a series of input buttons (e.g., push buttons) for the user to control the mixing process.

[0046] 4 illustrates an exemplary drug reconstitution method 400, according to various embodiments, which includes the following steps: Step 410: Physically connect the vessel to the system (as noted above, physical connection does not necessarily mean fluid connection); Step 420: Mixing the diluent component and the drug product component, such as by utilizing the above or other suitable process; Step 430: Mixing the IVSS component and the saline component, such as by utilizing the above or other suitable steps; Step 440: Add the IVSS / saline mixture to the final drug product container, such as by utilizing the above or other suitable steps; Step 450: Adding the drug product / diluent to the final drug product container, such as by utilizing the above or other suitable steps; and Step 460: Remove the final drug product container for use and / or storage.

[0047] The above steps are exemplary and may be modified and / or performed in a different order than described above. Some or all of the above may be performed by or under the direction of a controller, including, for example, controller 295 or controller 395 described above. In some embodiments, a controller may be programmed to perform some or all of the above steps.

[0048] In some instances, the IVSS may be provided as a percentage of the total volume of the solution. In these instances, a suitable amount of IVSS may range from about 2% to about 15% (e.g., about 1 mL in a 50 mL container to about 25 mL in a larger 270 mL container). The IVSS can also act as a pretreatment surfactant or buffer component to prevent drug adsorption to the container walls. For example, if the container is not adequately and properly coated with IVSS, the highly potent nature of some drugs being administered can lead to the undesirable risk of drug molecules adhering to or adsorbing onto the interior walls of the container. Drug adsorption to the walls of the delivery container can adversely affect the drug dosage. In such situations, it may be desirable to utilize the exemplary process described in the previous paragraph.

[0049] In some examples, the IVSS may contain polysorbate. In some examples, the IVSS formulation may contain about 1.25 M lysine monohydrochloride, 25 mM citric acid monohydrate, 0.1% (w / v) polysorbate 80, and have a pH of about 7.0. In other examples, the IVSS 54 may contain a similar formulation but also contain at least about 0.9% NaCl and about 0.001 to about 0.1% (w / v) polysorbate 80. It is understood that different BiTEs require different final percentages of IVSS 54 in the delivery container. This percentage may vary from about 0.5% to about 12% of the final volume in the delivery container. Furthermore, citrate may increase the risk of glass delamination when filled into glass vials. If citrate is required for drug product stabilization (determined on a product-by-product basis), the delivery container may be constructed from CZ or other plastic compositions. Other examples of components for a suitable IVSS are also possible. An appropriate IVSS concentration prevents protein-plastic interaction and / or surface adsorption, more particularly at the lower end of the concentration range where even small losses can potentially alter the effective amount. The following table shows exemplary component concentrations for various IVSS concentrations.

[0050] [Table 1]

[0051] By providing the components in selectively connectable containers, it may no longer be necessary to prepare a needle and syringe assembly to inject one component into another container, ensure that the prepared needle and syringe assembly is sterile, and / or ensure that the correct volumes or amounts of components are added together.

[0052] Some conventional systems may provide a delivery container overfilled with saline when more saline than required for the dose is provided in the delivery container. These systems may require removal of a certain amount of saline prior to preparation of the drug dose, which may require the preparation of a sterile extraction tool (e.g., a needle and syringe assembly) to carefully extract the correct amount of saline. Conversely, the disclosed system may even eliminate this process, as the container is prefilled with the required amount of ingredients. Additionally, the risk of needlestick injuries due to the transfer of ingredients may also be reduced or mitigated.

[0053] Additionally, many or all of the above steps may be automated or semi-automated or reduced in time / extent, potentially saving time and effort for those preparing and / or using the drug.

[0054] As described above, the drug product container contains a predetermined amount (e.g., from about 2 mcg to about 100 mcg) of drug product or active pharmaceutical ingredient (the "API") in powder form (i.e., lyophilized form) that requires reconstitution, depending on the BiTE® and container size, in the illustrated example. In other examples, the drug product may be in liquid form and may not require reconstitution. Nevertheless, since the system contains the exact amount of drug product, there is no need to add additional amounts to the drug product in a sterile environment. In some examples, the API may optionally be in the form of a half-life extended ("HLE") BiTE® and / or a monoclonal antibody ("mAb") for intravenous administration. These HLE BiTEs contain an antibody Fc region that advantageously provides different drug properties such as a longer half-life and an extended half-life. Thus, such an API may be preferred as it can maintain the level of patient protection over a relatively long period. Nevertheless, in other examples, the API may be in the form of a standard BiTE to be administered in a specialized medical environment.

[0055] In some embodiments, the drug delivery system may have a built-in reconstitution subsystem for diluting the lyophilized drug into a liquid form. Certain such embodiments may include a diluent reservoir for storing the diluent solution and a lyophilized reservoir for storing the lyophilized compound separately from the diluent solution. Additionally, a fluid drive mechanism may be included for mixing the diluent solution in the diluent reservoir with the lyophilized compound in the lyophilized reservoir. In some embodiments, the fluid drive mechanism may move the diluent solution from the diluent reservoir to the lyophilized reservoir and / or provide any circulation and / or agitation necessary to achieve complete reconstitution. In some embodiments, an additional reservoir for the final reconstituted drug may be included or may serve as a delivery reservoir from which the reconstituted drug is released to the patient, while in other embodiments, the lyophilized reservoir may serve as a delivery reservoir. While in certain embodiments, the reconstitution subsystem may be physically integrated into the drug delivery system, in other embodiments, the reconstitution subsystem may constitute a separate unit in fluid communication with the drug delivery system. Having a separate unit may simplify the reconstitution process for healthcare providers in certain cases.

[0056] The drug product container may be in the form of an IV bag, vial, pre-filled syringe, or similar container including a reconstitution container body defining an internal volume. The internal volume may be sterile. In some approaches, the reconstitution container adapter may also be a CSTD that fits, engages, and / or mates with the vial adapter (or, in instances where the pre-filled reconstitution container is in the form of a syringe, the container adapter may be a needle). Additionally or alternatively, the drug product may be bulk lyophilized and loaded into cartridges or containers typically used for administration with an IV pump. If necessary, dehydrated forms of IVSS, NaCl, and any other components required for the final administration solution may be bulk lyophilized and loaded into cassettes for long-term storage.

[0057] The pre-filled diluent container contains a predetermined amount of diluent (e.g., water for injection without preservatives or "WFI") (e.g., from about 0.5 mL to about 10 mL) to be added to the pre-filled drug product container for reconstitution of the drug product. In some examples, WFI preserved with benzyl alcohol (or containing any other optional preservative) may be used.

[0058] As already described, in some examples, the pre-filled drug product container may be in the form of a pre-filled syringe containing the drug product. In these examples, the drug product may be in the form of a liquid BiTE® formulation used in combination with a monoclonal antibody (mAb). In these examples, the drug product may advantageously simplify and / or improve the supply chain and manufacturing control, and further enable a more compact commercial packaging that occupies less space in the storage system in a medical facility, without using a vial adapter system (such as the CSTD described above), when more conventional needle-syringe injection / delivery into the container is preferred, and may be added directly to the delivery container. In these examples, the pre-filled drug product vial may or may not need to be reconstituted prior to transfer of the drug product to the delivery container.

[0059] The system may be distributed and / or sold as a common kit package, but other suitable distribution / package is also appropriate. The drug product may be in the form of a bispecific T cell engager with an extended half-life (BiTE®), but other drug products are also appropriate. The diluent includes water for injection ("WFI"), but other diluents may be appropriate in some cases. The container may be a soft bag, such as an IV bag, but other containers may be appropriate in some cases. In some examples, one or more of the containers are in the form of a 250 mL 0.9% sodium chloride IV bag constructed from plastic or other materials, such as polyolefin, non-DEHP (diethylhexyl phthalate), PVC, polyurethane, or EVA (ethylene vinyl acetate), and can be filled up to a volume of about 270 mL, taking into account potential water loss during long-term storage.

[0060] The contents of the container may then be gently stirred, vortexed, and / or inverted during some or all of the above steps to mix the ingredients, thereby forming the desired mixture. Similarly, the mixture may be visually inspected for imperfections and / or to ensure proper mixing has occurred.

[0061] The system may be used to provide intravenous, subcutaneous, intra-arterial, intramuscular, and / or epidural delivery techniques. Use of the system may reduce patient anxiety and / or confusion due to reduced preparation complexity and waiting times caused by the drug preparation process.

[0062] In some examples, the prefilled delivery container is in the form of an IV drip bag constructed from plastic or other materials, e.g., a 250 mL 0.9% sodium chloride IV bag constructed from a suitable material, such as polyolefin, non-DEHP (diethylhexyl phthalate), PVC, polyurethane, or EVA (ethylene vinyl acetate), which can be filled to a volume of approximately 270 mL to account for potential moisture loss during long-term storage. Other examples of suitable delivery containers are possible, such as glass bottles or containers. Exemplary suitable prefilled delivery containers are described in U.S. Patent Application Nos. 62 / 804,447, filed February 12, 2019, and 62 / 877,286, filed July 22, 2019, the entire contents of each of which are incorporated by reference.

[0063] At least one of the delivery container adapters may be a closed drug transfer system ("CSTD") that allows for the transfer of drugs and / or fluids into the container body. Exemplary CSTD devices may include the OnGard CSTD, BD PhaSeal CSTD components, Equadelass CSTD, Codon CSTD, etc., offered by B. Braun Medical Inc. Additionally, non-closed drug transfer systems may be used, such as vial and bag adapters from West Pharmaceuticals. Other examples are possible. The pre-filled delivery container may include any number of delivery container adapters with different specifications (e.g., port sizes) that accommodate the use of different drug product vials.

[0064] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used in conjunction with drugs, including, but not limited to, the drugs identified below and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may refer to any type of pharmaceutical or therapeutic material, including traditional and non-traditional medicines, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also encompassed. Drugs may be in liquid form, lyophilized form, or reconstituted from a lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0065] The drug is contained in a reservoir. Optionally, the reservoir is a primary container that is either filled or pre-filled with the drug for treatment. The primary container can be a vial, cartridge, or pre-filled syringe.

[0066] In some embodiments, the reservoir of the drug delivery device may be filled with a colony stimulating factor such as granulocyte colony stimulating factor (G-CSF), or the device can be used with them. Such G-CSF formulations include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF).

[0067] In other embodiments, the drug delivery device may contain or be used in conjunction with an erythropoiesis-stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, the ESA is an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis-stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), and Binocrit® (epoetin alfa). Epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin, and molecules or variants or analogs thereof.

[0068] Among certain exemplary proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, related proteins, etc., including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin-binding proteins, peptibodies, related proteins, etc., including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which particularly inhibit activities mediated by binding of IL-4 and / or IL-13 to their receptors. Interleukin 1-receptor 1 ("IL1-R1")-specific antibodies, peptibodies, related proteins, etc.; Ang2-specific antibodies, peptibodies, related proteins, etc.; NGF-specific antibodies, peptibodies, related proteins, etc.; CD22-specific antibodies, peptibodies, related proteins, etc., particularly dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, e.g., the human form of epratuzumab (CAS Registry Number 501423-23-0). human CD22-specific antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly including, but not limited to, human CD22-specific IgG antibodies, such as humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, including, but not limited to, anti-IGF-1R antibodies; IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including, but not limited to, anti-IGF-1R antibodies; B-7-related protein 1-specific antibodies, peptibodies, and related proteins, including, but not limited to, those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1 on activated T cells, including, but not limited to, a B7RP-specific fully human monoclonal IgG2 antibody; HuMax, e.g., 146B7; IL-15 specific antibodies, peptibodies, related proteins, etc., including, but not limited to, IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies; human IFNIFN-γ specific antibodies, peptibodies, related proteins, etc., including but not limited to those containing γ-specific antibodies and fully human anti-IFN-γ antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., and other TALL-specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, etc., including those targeting the HGF:cMet axis (HGF / SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter factor (HGF / SF); TRAIL-R2 specific antibodies, peptibodies, related proteins, etc.; activin A specific antibodies, peptibodies, proteins, etc.; TGF-β specific antibodies, peptibodies, related proteins, etc.; amyloid-β protein specific antibodies, peptibodies, related proteins, etc.; c-Kit specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to c-Kit and / or other stem cell factor receptors; OX40L specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon β-1a), Bexxar® (tositumomab, anti-CD22 monoclonal antibody), Betaseron® (interferon-β), Campath® (alemtuzumab, anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-α4β7mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alpha), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu (erbB2) receptor mAb), Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Vectibix® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargramostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lynfotostat B, belimumab, anti-BlyS mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP 870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCimhR3 (Nimotuzumab), Omnitarg (Pertuzumab, 2C4), Osidem (registered trademark) (IDM-1), OvaRex (registered trademark) (B43.13), Nuvion (registered trademark) (Visilizumab), Cantuzumab mertansine (huC242-DM1), NeoRecormon (registered trademark) (Epoetin beta), Neumega (registered trademark) (Oprelvekin, human interleukin-11), Orthoclone OKT3 (registered trademark) (Muromonab-CD3, anti-CD3 monoclonal antibody), Procrit (registered trademark) (Epoetin alpha), Remicade (registered trademark) (Infliximab, anti-TNFα monoclonal antibody), Reopro (registered trademark) (Abciximab, anti-GP lIb / Ilia receptor monoclonal antibody), Actemra (registered trademark) (anti-IL6 receptor mAb), Avastin (registered trademark) (Bevacizumab), HuMax-CD4 (Zanolimumab), Rituxan (registered trademark) (Rituximab, anti-CD20 mAb), Tarceva (registered trademark) (Erlotinib), Roferon-A (registered trademark) (Interferon α-2a), Simulect (registered trademark) (Basiliximab), Prexige (registered trademark) (Lumiracoxib), Synagis (registered trademark) (Palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Patent No. 7,153,507), Tysabri (registered trademark) (Natalizumab, anti-α4 integrin mAb), Valortim (registered trademark) (MDX-1303, anti-anthrax protective antigen mAb), ABthrax (trademark), Xolair (registered trademark) (Omalizumab), ETI211 (anti-MRSA mAb), IL-1 trap (Fc portion of human IgG1 and extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (Ig domain of VEGFR1 fused to IgG1 Fc), Zenapax (registered trademark) (Daclizumab), Zenapax (registered trademark) (Daclizumab, anti-IL-2Rα mAb), Zevalin (registered trademark) (Ibritumomab tiuxetan), Zetia (registered trademark) (Ezetimibe), Orencia (registered trademark) (Abatacept, TACI-Ig), anti-CD80 monoclonal antibody (Galiximab), anti-CD23mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO 148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatumumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (cetuximab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb, and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin B C mAb MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis phase 1 fibrinogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO 1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO 95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106 (ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβmAb (GC-1008), anti-TRAIL receptor-2 human mAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, and anti-ZP3 mAb (HuMax-ZP3).

[0069] In some embodiments, the drug delivery device may contain or be used in conjunction with a sclerostin antibody, such as, but not limited to, romosozumab, brosozumab, or BPS 804 (Novartis), or in other embodiments, a monoclonal antibody (IgG) that binds to human proprotein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9-specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including but not limited to, OncoVEXGALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain, or be used in conjunction with, an endogenous tissue inhibitor of metalloproteinase (TIMP), such as, but not limited to, TIMP-3. Antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab, and bispecific antibody molecules targeting the CGRP receptor and other headache targets, may also be delivered using the drug delivery devices of the present disclosure. Additionally, bispecific T cell engager (BiTE®) antibodies, such as, but not limited to, a half-life extended BiTE comprising an antibody Fc region, BLINCYTO® (blinatumomab), can be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery devices may contain or be used with APJ large molecule agonists, such as, but not limited to, apelin or analogs thereof.In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery devices of the present disclosure.

[0070] Drug delivery devices, assemblies, components, subsystems, and methods have been described from the perspective of exemplary embodiments, but are not limited thereto. This detailed description should be construed as illustrative only and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments are still within the scope of the claims that define the invention disclosed herein.

[0071] Those skilled in the art will understand that various modifications, changes, and combinations can be made to the above embodiments without departing from the spirit and scope of the invention disclosed herein, and such modifications, changes, and combinations are construed to be within the scope of the concept of the invention.

Claims

1. A method for preparing a drug for delivery, comprising: providing a diluent contained in a diluent container; providing a drug product contained in a drug product container; providing a physiological saline solution contained in a physiological saline container; providing an intravenous stabilization solution (IVSS) contained in an IVSS container; providing a fluid path system that physically connects the diluent container, the drug product container, the physiological saline container, and the IVSS container, wherein the fluid path system has a storage configuration in which the diluent container and the drug product container are not in fluid communication with each other and the physiological saline container and the IVSS container are not in fluid communication with each other, a first mixing configuration in which the diluent container and the drug product container are in fluid communication with each other via a first portion of the fluid path system, and a second mixing configuration in which the physiological saline and the IVSS container are in fluid communication with each other via a second portion of the fluid path system; adjusting the fluid path system from the storage configuration to the first mixing configuration to urge at least a portion of the diluent from the diluent container and / or at least a portion of the drug product from the drug product container to form a drug product / diluent mixture; controlling at least one valve to fluidly isolate the first portion of the fluid path system from the second portion of the fluid path system when the fluid path system is in the first mixing configuration and / or the second mixing configuration. A method comprising the above steps.

2. The method according to claim 1, wherein adjusting the fluid path system from the storage configuration to the first mixing configuration includes opening a valve.

3. The method according to claim 1, wherein adjusting the fluid path system from the storage configuration to the first mixing configuration includes removing a clamp.

4. Further comprising adjusting the fluid path system to the second mixing configuration to urge at least a portion of the physiological saline from the physiological saline container and / or at least a portion of the IVSS from the IVSS container to form a physiological saline / IVSS mixture. The method according to any one of claims 1 to 3.

5. The method according to claim 4, further comprising the step of adjusting the fluid path system from the storage configuration to a third mixing configuration so as to urge at least a portion of the drug product / diluent mixture and at least a portion of the saline / IVSS mixture into fluid communication with each other.

6. Providing a pump selectively coupled to the fluid path system; Adjusting the position of the pump between a first position between the diluent container and the drug product container and a second position between the saline container and the IVSS container in at least two of the first mixing configuration, the second mixing configuration, and the third mixing configuration; The method according to claim 5, further comprising.

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