System and method for reconstruction of drug delivery device

Abstract

To provide a method for preparing drug to be delivered, and a drug delivery system for achieving the same method.SOLUTION: A method for preparing drug for delivery comprises: preparing a diluent stored in a diluent container; and preparing a drug product stored in a drug product container. The method may further comprise: fluid connecting the diluent container and the drug product container. In addition, the method may comprise energizing at least part of the diluent into the drug product container from the diluent container by a pump, for reconstructing the drug product at least partially.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority to U.S. Provisional Application No. 62 / 923,179, 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 a medical facility (e.g., a hospital facility, an outpatient facility, and / or a pharmacy).

[0004] When reconstituting these drugs for administration, it is particularly important to maintain a sterile environment so as not to degrade the quality of the drug, compromise the sterility of the drug, or otherwise impair the quality of the drug. Additionally, some classes of drugs, such as bispecific T cell engagers, may require extremely precise amounts of the drug product and / or other fluids necessary for administration to prevent the drug product from becoming toxic. Often, healthcare professionals must prepare the drug by strictly following a set of procedures to ensure that a sterile environment is maintained, which may include following the correct procedure, and that the correct amounts of the components 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 procedures and requirements, the reconstitution process can be time-consuming, cumbersome, and may result in an unacceptable or undesirable error rate.

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

[0006] In addition, due to current regulatory requirements implemented by the National Institute for Occupational Safety and Health (NIOSH), certain tumor products are included in a hazardous drug list that requires the use of additional engineering controls, such as a closed drug transfer system (CSTD), as an additional means of protection. Also, regardless of whether a drug is on the NIOSH list, it may be advantageous to utilize a CSTD and / or other components / systems to minimize or prevent unwanted emissions of fumes or other exposures into the air.

[0007] As described in more detail below, the present disclosure describes a system and method for reconstituting a drug delivery device that embodies advantageous alternatives to existing systems and methods, and can 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] Aspects of the present disclosure provide a method for preparing a drug for delivery. The method may include: (a) providing a diluent contained in a diluent container; (b) providing a drug product contained in a drug product container; (c) fluidly connecting the diluent container and the drug product container; and (d) urging at least a portion of the diluent from the diluent container into the drug product container by a pump to at least partially reconstitute the drug product.

[0009] Additional aspects of the present disclosure provide a drug delivery system including a diluent container, a drug product container, at least one fluid path connector, and a pump. The diluent container may contain a diluent, and the drug product container may contain a drug product. At least one fluid path may be configured to at least selectively fluidly connect the diluent container and the drug product container. The pump may be functionally connected to the fluid path connector and configured to urge at least a portion of the diluent from the diluent container into the drug product container to at least partially reconstitute the drug product.

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

Brief Description of the Drawings

[0011]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

BRIEF DESCRIPTION OF THE DRAWINGS

[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 assist in understanding various embodiments of the present invention. Also, elements that are common but well understood and useful or necessary in commercially realizable embodiments 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 as to order is not actually necessary. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as would be given by those skilled in the art to such terms and expressions, unless a different specific meaning is set forth herein.

[0013] The present disclosure generally relates to a diluent container containing a diluent, a drug product container containing a drug product, a fluid path connector that at least selectively fluidly connects the diluent container and the drug product container, and a pump that is functionally connected to (e.g., operably connected to) the fluid path connector and configured to urge at least a portion of the diluent from the diluent container into the drug product container to at least partially reconstitute the drug product. The present disclosure also relates to a drug delivery device and a method of providing a drug delivery device that may include a solution container containing a predetermined amount of physiological saline and a predetermined amount of intravenous stabilization solution ("IVSS"). In such a system, the pump can urge at least a portion of the predetermined amount of physiological saline and the predetermined amount of IVSS from the solution container into the drug product container.

[0014] For example, the drug product can be bulk freeze-dried and filled into a cartridge typically used for administration with an IV pump. If desired, the dehydrated form of IVSS, NaCl, and any other components required for the final administration solution can be bulk freeze-dried for long-term storage and filled into a cassette. As part of a kit for any administration cartridge, a complementary sterile water for injection (sWFI) cartridge can be provided, and the sterile water for injection (sWFI) acts as a diluent for reconstituting the product for administration. Reconstitution can be performed in a simple and elegant manner using the administration pump itself to perform the reconstitution without additional accessories. The sWFI cartridge can then be coupled to the IV pump, as seen in FIG. 6. For example, the two cartridges can be connected via a simple luer adapter or an integral connection of the cartridges. A simple button or mode setting for a "reconstitution mode" can then be selected, which, as seen in FIG. 6, instructs the pump to remove the contents of the sWFI cartridge and send them into the Lyo cartridge to reconstitute the freeze-dried product. After the contents are removed, the fully reconstituted cassette can be connected to the pump for administration to a patient. This preparation may be completed at a pharmacy or at another location such as an HCP's treatment room or the patient's home.

[0015] Turning to FIGS. 1 and 2, according to these various embodiments, a drug delivery system 1 or kit and a corresponding method of preparing a drug delivery device using the drug delivery system 1 are provided. A healthcare professional, caregiver, or patient can use the drug delivery system 1 to prepare a drug delivery device for delivery to a patient. The drug delivery system 1 differs from conventional systems in that many of the components contained within the system 1 are pre-filled and / or pre-mixed in the correct dosages. As a result, while ensuring that the correct amount of components is administered, the preparation of the drug delivery device by a healthcare professional, caregiver, or patient is reduced. The system 1 may be used to provide intravenous, subcutaneous, intra-arterial, intramuscular, and / or epidural delivery techniques. By using this system 1, patient anxiety and / or confusion may be reduced due to a decrease in the complexity and waiting time of the preparation resulting from the drug preparation process. Additionally, the system 1 may allow a healthcare provider, pharmacist, patient, and / or other individual 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 1 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 1 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.

[0016] The drug delivery system 1 shown in FIG. 1 generally includes a diluent container 10 that houses a diluent 12, a drug product container 20 that houses a drug product 22, a fluid path connector 30 that at least selectively fluidly connects the diluent container 10 and the drug product container 20, and a pump 40 that is functionally connected to the fluid path connector 30 and configured to urge at least a portion of the diluent 12 from the diluent container 10 into the drug product container 20 to at least partially reconstitute the drug product 22. The drug delivery system 1 shown in FIG. 1 may also include a solution container 50 that houses a predetermined amount of physiological saline 52 and a predetermined amount of intravenous stabilization solution (“IVSS”) 54. The predetermined amounts of physiological saline 52 and IVSS 54 shown in the figure are mixed and generally form an aqueous solution, although other configurations may also be appropriate. In such a system, the pump 40 can urge at least a portion of the predetermined amount of physiological saline 52 and the predetermined amount of IVSS 54 from the solution container into the drug product container.

[0017] The pump 40 shown in FIG. 1 may be a peristaltic pump, a positive displacement pump, or any other suitable type of pump that is functionally connected to the fluid path connector 30. For example, the fluid path connector 30 may be a tube having a portion looped to be substantially circular, and the removable pump head 42 may be a peristaltic pump head having a tube portion and a rotating component that travels along a substantially circular path and, in the process, constricts the tube portion to urge fluid to move through the tube. In such a configuration, the removable pump head 42 is functionally connected to the fluid path connector 30 even though the fluid moving through the tube does not directly contact the components of the pump head 42. As another example, the pump may have components that directly contact the fluid moving through the tube. As another example, any suitable pump may be used. Additionally, or alternatively, instead of a pump, the system may utilize another configuration or process for mixing, such as a negative pressure arrangement between various containers, that urges the diluent 12 into the drug product container 20.

[0018] The pump 40 may be automatically activated when one or more of the respective containers 10, 20, 50 are coupled to each other, or the pump 40 may be activated by an activation button 44 or other suitable component. For example, the activation button 44 may be functionally connected to an internal controller and / or electromechanical components that operate the pump 40.

[0019] The fluid path connector 30 may include several different tubes, such as a tube 30a coupled to the pump head 42, a tube 30b fluidly coupled to the diluent container 10 via the stake connector 34b, a tube 30c fluidly connected to the drug product container 20 via the stake connector 34c, and / or a tube 30d fluidly connected to the solution container 50 via the stake connector 34d. The connectors 32b, 32c, 32d may be quick-connect sterile connectors having respective sub-components that selectively mate with each other while maintaining sterility or another desired cleanliness standard. For example, the quick-connect sterile connectors may snap-fit, interlock, or screw together, and the quick-connect sterile connectors may have sheathed and covered components where the sheath or covering is removed upon connection, and / or the quick-connect sterile connectors may have a luer lock configuration or a modified luer lock configuration. During one exemplary operation, the diluent container 10 is selectively coupled to the drug product container 20 via the connectors 32b, 32c, and the pump head 42 operates to urge diluent 12 from the diluent container 10 to interact with the drug product 22 within the drug product container. Next, during another step in the exemplary operation, the diluent container 10 is disconnected from fluid connection with the pump head 42 via the connector 32b, and then the solution container 50 is fluidly coupled to the tube 30a via the connector 32d. The pump head can then urge saline 52 and IVSS 54 into the drug product container 20 such that the various components (drug product 22, diluent 12, saline 52, and IVSS 54) are well mixed and available for delivery to the patient. As a more specific example, when the drug product container 20 has a desired mixture of desired components, the drug product container 20 may be fluidly connected to the pump head 42 for delivery to the patient via a venous line, port, catheter, or other suitable drug delivery component.

[0020] Each of the containers 10, 20, 50 shown in FIG. 1 is fluidly coupled to each other in pairs at a time, but other suitable configurations may be used, such as when the tube 30d is fluidly connected to the tube 30b, and in between, the tube 30b is also fluidly connected to the tube 30c. For example, the tube 30d may be fluidly connected to the stake 34b such that the pump biases the diluent from the diluent container 10 until the diluent container 10 is empty or substantially empty, and then the contents of the solution container 50 are biased into the drug product container 20 through various components of the fluid path connector 30 by the vacuum force from the pump 42.

[0021] Additionally, or alternatively, the direction in which each of the components 12, 22, 52, 54 is drawn and the containers 10, 20, 50 in which the components are mixed may be different. For example, the diluent 12 may be biased into the drug product container 20 as described above, and then the drug product 22 / diluent 12 mixture may be biased into the solution container 50 for mixing with the solution 52 and the IVSS 54. The connectors 32b, 32c, 32d allow for a flexible configuration for the user.

[0022] In some examples, the IVSS 54 may be provided as a percentage of the total volume of the solution. In these examples, a suitable amount of the IVSS 54 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, see step 202 in FIG. 4). The IVSS 54 can also act as a pretreatment surfactant or buffering component to prevent the adsorption of the drug to the walls of the container 50. For example, if the container is not adequately and properly coated with the IVSS 54, due to the highly potent nature of some of the drugs being administered, there may be an undesirable risk that drug molecules will adhere or adsorb to the inner walls of the container. If the drug adsorbs to the walls of the delivery container, it may adversely affect the dosage of the drug. In such situations, it may be desirable to utilize the exemplary steps described in the previous paragraph.

[0023] In some examples, the IVSS54 may include polysorbate. In some examples, the IVSS54 formulation may include 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 IVSS54 includes a similar formulation but may also have 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 proportions of IVSS54 in the delivery container. This proportion can vary between about 0.5% and about 12% of the final volume in the delivery container. Further, citrate may increase the risk of glass delamination when filled in a glass vial. If citrate is required for the stabilization of the drug product (determined for each product), the delivery container may be constructed from a crystal zenith (CZ) polymer or other plastic composition. Other examples of components for a suitable IVSS54 are also possible. A suitable IVSS54 concentration prevents protein-plastic interactions and / or surface adsorption, more specifically, at the lower limit of the concentration range that can potentially vary the effective amount even with a slight loss. The following table shows exemplary component concentrations for various IVSS concentrations.

[0024]

Table 1

[0025] By preparing components 12, 22, 52, 54 in a selectively connectable container, preparing a needle and syringe assembly, injecting a component into another container, it may no longer be necessary to ensure that the prepared needle and syringe assembly is sterile and / or that the correct volume or amount of components are added together.

[0026] Some conventional systems may provide a delivery container that is overfilled with saline when more saline is provided to the delivery container than is necessary for the dosage. In these systems, it may be necessary to prepare a sterile withdrawal tool (e.g., a needle and syringe assembly) and carefully withdraw an exact amount of saline prior to preparing a drug dosage, where it may be necessary to remove a certain amount of saline. Conversely, the disclosed System 1 further eliminates this process since the delivery container is pre-filled with the required amount of components. Additionally, the risk of needle sticks due to component transfer may also be reduced or mitigated.

[0027] Additionally, many or all of the above steps may be automated or semi-automated, or the time / scope may be reduced, thereby potentially saving time and labor for the person preparing and / or using the drug.

[0028] As described above, the drug product container 20 contains a predetermined amount (e.g., from about 2 mcg to about 100 mcg) of drug product 22 or active pharmaceutical ingredient (「API」) depending on the BiTE (registered trademark) and container size, which in the illustrated example is in powder form (i.e., lyophilized form) that requires reconstitution. In other examples, the drug product 22 may be in liquid form and may not require reconstitution. Nevertheless, since System 1 contains an exact amount of drug product 22, there is no need to add additional amounts to the drug product 22 in a sterile environment. In some examples, the API may, optionally, be in the form of a half-life extended (「HLE」) BiTE (registered trademark) and / or a monoclonal antibody (「mAb」) for IV 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 since it can maintain a level of patient protection over a relatively long period of time. Nevertheless, in other examples, the API may be in the form of a standard BiTE to be administered in a specialized medical setting.

[0029] In some embodiments, the drug delivery system 1 may include a built-in reconstitution subsystem configured to dilute the lyophilized drug into a liquid form. In certain such embodiments, a diluent reservoir for storing the dilution solution may be included, and a lyophilized product reservoir for storing the lyophilized compound separately from the dilution solution may be included. Further, a fluid drive mechanism for mixing the dilution solution in the diluent reservoir with the lyophilized compound in the lyophilized product reservoir may be included. In some embodiments, the fluid drive mechanism may move the dilution solution from the diluent reservoir to the lyophilized product reservoir and / or provide any circulation and / or agitation necessary to obtain complete reconstitution. In some embodiments, a reservoir for the additional reconstituted final drug may be included and may serve as a delivery reservoir from which the reconstituted drug is released to the patient. On the other hand, in other embodiments, the lyophilized product reservoir may serve as the delivery reservoir. In certain embodiments, the reconstitution subsystem may be physically incorporated into the drug delivery system 1, while in other embodiments, the reconstitution subsystem may comprise a separate unit in fluid communication with the drug delivery system 1. Having a separate unit may simplify the reconstitution process for the healthcare provider in certain cases.

[0030] The drug product container 20 may be in the form of an IV bag, vial, pre-filled syringe, or similar container including a reconstitution container body that defines 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 couples to a vial adapter (or, in the example 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 22 may be bulk lyophilized and filled into a cartridge or container typically used for administration with an IV pump. If necessary, the dehydrated forms of IVSS, NaCl, and any other components required for the final administration solution may be bulk lyophilized for long-term storage and filled into a cassette.

[0031] The pre-filled diluent container 10 contains a predetermined amount of diluent 12 (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 20 for the reconstitution of the drug product 22. In some examples, WFI preserved with benzyl alcohol (or containing any other optional preservative) may be used.

[0032] 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 conjunction with a monoclonal antibody (mAb). In these examples, the drug product may advantageously simplify and / or improve the supply chain and manufacturing management, and further enable a more compact commercial packaging that occupies less space in the storage system in a healthcare 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. 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.

[0033] System 1 may be distributed and / or sold as a common kit package 60, although other suitable distribution / packages are also appropriate. The pharmaceutical product may be in the form of a bispecific T cell engager with an extended half-life (BiTE®), although other pharmaceutical products are also appropriate. The diluent 12 includes water for injection (“WFI”), although other diluents may be appropriate in some cases. The containers 10, 20, 50 may be soft (e.g., flexible) bags such as IV bags, although other containers may be appropriate in some cases. In some examples, one or more of the containers 10, 20, 50 are 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 a polyolefin, non-DEHP (diethylhexyl phthalate), PVC, polyurethane, or EVA (ethylene vinyl acetate), and can be filled to a volume of approximately 270 mL to account for potential water loss during long-term storage.

[0034] Next, during some or all of the above steps, the contents of the container may be gently stirred, vortexed, and / or inverted to mix the components, thereby forming the desired mixture. Similarly, the mixture may be visually inspected to check for incompleteness and / or to confirm that proper mixing has occurred.

[0035] When the drug product 22 and other ingredients are mixed as desired, the drug product container 20 (or any container holding the mixed drug product 22 and other ingredients) may be delivered to the patient using the pump 40. For example, the same pump head 42 may be used, with one end connected to the container 10 and the other end connected to the patient. Alternatively, a new unused pump head 42 may be used for this next step. The pump head 42 may be disposable or reusable. Similarly, the rest of the pump 40 may also be reusable or disposable (preferably reusable for environmental and cost advantages). The pump may also have different modes, such as a "reconfiguration mode" in which the pump operates under one set of parameters and a "delivery mode" in which the pump operates under another set of parameters. Alternatively, or additionally, the pump may operate in different modes or speeds or other parameters by control of the pump itself or by control of another device such as a smartphone or other suitable device wirelessly paired to it.

[0036] The pump 40 may include a door 48 and a lock 46 to facilitate removal and insertion of the pump head 42 components and / or for safety reasons during operation. The pump 40 may be configured not to operate unless the door 48 and lock 46 are in the desired positions.

[0037] Figure 2 shows the pump 40 in an exemplary drug delivery mode, in which the drug product 22 is dissolved and the mixed components 12, 22, 52, 54 are uniformly distributed throughout the container 20. The reconfiguration mode may appear similar or the same as the configuration shown in Figure 2, but additional containers are coupled together.

[0038] The fluid path connector 30 shown in FIG. 1 may be connected to one of the diluent container 10 and the solution container 50 at any time depending on which of these containers is transferring fluid to the drug product container 20 at the present time. The drug delivery system 300 shown in FIG. 7 includes many components that are similar or identical to those shown in FIG. 1, except that the system 300 additionally includes a valve 360. As will be described in more detail below, the valve 330 may allow the fluid path connector 330 to remain connected to both the diluent container 310 and the solution container 350 throughout the reconfiguration process. Elements of the drug delivery system 300 that are not described in further detail below may have a configuration, function, and / or structure that is similar or identical to the corresponding numbered elements described above with respect to the drug delivery system 1 shown in FIG. 1.

[0039] The valve 360 may be configured to selectively fluidly connect one of the diluent container 310 and the solution container 350 to the drug product container 320. By way of example, the valve 360 may have at least two inlets or ports fluidly connected to the diluent container 310 and the solution container 350, respectively, via tubes 330e and 330f. The valve 360 may additionally have at least one outlet or port fluidly connected to the pump head 342 via tube 330a. As a more specific example, the valve 360 may include a movable or actuatable component that opens a passage between one of the two inlets and the outlet while closing a passage between the other of the two inlets and the outlet depending on its position or state. As an even more specific example, the valve 360 may be a three-way valve including, for example, a three-way ball valve having an L-shaped fluid passage inside a rotor. As another example, the valve 360 may include an electronically controllable element such as a solenoid for selectively fluidly connecting one of the diluent container 310 and the solution container 350 to the drug product container 320. As another example, a hydrophilic filter may be incorporated into the valve 360. The hydrophilic filter may be configured to forcibly draw or directly extract fluid from the other of the diluent container 310 and the solution container when the fluid from one of the diluent container 310 and the solution container is depleted. As a more specific example, the hydrophilic filter may be configured to allow the passage of fluid but prevent the passage of gas such that when the fluid from one of the diluent container 310 and the solution container is depleted, the hydrophilic filter may close the passage to the empty container and, in at least some configurations, direct the suction force from the pump 340 to extract fluid from the other of the diluent container 310 and the solution container.

[0040] As shown in FIG. 7, the valve 360 may be a component separate from the pump 340 and the pump head 342. In other embodiments, the valve 360 may be incorporated into the pump 340 and / or the pump head 342.

[0041] During one exemplary reconstitution process, valve 360 may be configured to fluidly connect diluent container 310 to drug product container 320, and pump head 342 may be driven by pump 340 to urge diluent 312 from diluent container 310 to interact with drug product 322 within drug product container 320. Next, during another step in the exemplary operation, valve 360 may be configured to fluidly disconnect the diluent container from drug product container 320 and, instead, fluidly connect solution container 350 to drug product container 320. Subsequently, pump head 342 may be driven by pump 340 to urge saline 352 and IVSS 354 into drug product container 320 such that the various components (e.g., drug product 322, diluent 312, saline 352, and IVSS 354) are sufficiently mixed and available for delivery to a patient. When drug product container 320 has the desired mixture of desired components, drug product container 320 may be fluidly connected to pump head 342 for delivery to a patient via a venous line, port, catheter, or other suitable drug delivery component. In some embodiments, these drug delivery components may be connected to one of the ports of valve 360 used to connect valve 360 to diluent container 310 or solution container 350 during the reconstitution process or to another port of valve 360.

[0042] Turning to FIGS. 3-5, according to various embodiments, a drug delivery system 100 or kit and a corresponding method 200 for preparing a drug delivery device using drug delivery system 100 are provided. Many or all of the features of system 100 may be utilized in conjunction with many or all of the features of system 1. Additionally, many or all of the features of system 1 may be utilized in conjunction with many or all of the features of system 100.

[0043] 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 in the correct dosage amounts. As a result, while ensuring that the correct amount of components are administered, the preparation of the drug delivery device by a medical professional, caregiver, or patient is reduced. 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 decrease in the complexity and waiting time of the preparation caused by the drug preparation process.

[0044] Generally, as shown in FIG. 3, the drug delivery system 100 includes a pre-filled delivery container 102, a pre-filled drug product vial 110, and a pre-filled reconstitution container 120. More specifically, the pre-filled delivery container 102 includes a container body 103 that defines an internal volume 104, a delivery container adapter 105, and an IV line outlet 109 that enables a tube to be coupled for delivering a prescription drug. In some examples, the pre-filled delivery container 102 is in the form of an IV drip bag constructed from plastic or other materials, such as 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), and can be filled up to a volume of about 270 mL to account for potential water loss during long-term storage. Other examples of suitable delivery containers are possible, such as a glass bottle or container (see, e.g., FIG. 5). An exemplary suitable pre-filled delivery container 102 is described in U.S. Patent Application No. 62 / 804,447, filed on February 12, 2019, and U.S. Patent Application No. 62 / 877,286, filed on July 22, 2019, the entire contents of each of which are incorporated herein by reference.

[0045] The delivery container adapter 105 may be a closed drug delivery system ("CSTD") that enables the transfer of drugs and / or fluids into the container body 103. Exemplary CSTD devices may include, but are not limited to, the OnGuard CSTD provided by B.Braun Medical Inc, the BD PhaSeal CSTD components, the Equashield CSTD, the Codon CSTD, and the like. Additionally, non-closed drug delivery systems, such as vial and bag adapters from West Pharmaceuticals, may be used. Other examples are possible. The pre-filled delivery container 102 may include any number of delivery container adapters 105 having different specifications (e.g., port sizes) corresponding to the use of different drug product vials 110.

[0046] The pre-filled delivery container 102 contains a predetermined amount (e.g., a fixed amount) of excipient solution. For example, the pre-filled delivery container 102 can contain a predetermined amount of physiological saline 108 (e.g., 0.9% sodium chloride of about 50 mL to 500 mL, preferably about 110 mL or about 270 mL depending on the size of the container) and a predetermined amount of intravenous stabilization solution ("IVSS") 106. In some examples, the IVSS 106 may be provided as a percentage of the total volume of the solution. In these examples, the appropriate amount of IVSS 106 may range from about 2% to about 15% (e.g., about 1 mL in a 50 mL container 102 to about 25 mL in a larger 270 mL container, see step 202 in FIG. 4). In some examples, the pre-filled delivery container 102 may have a total volume of about 270 mL. The IVSS 106 can also act as a pretreatment surfactant or buffering component to prevent the adsorption of the drug to the walls of the container 102. For example, if the container 102 is not adequately and properly coated with the IVSS 106, due to the highly potent nature of some of the drugs being administered, there may be an undesirable risk that drug molecules will adhere or adsorb to the inner wall of the container 102. If the drug adsorbs to the wall 102 of the delivery container, it may adversely affect the dosage of the drug. In some examples, the IVSS 106 may contain polysorbate 80. In some examples, the IVSS 106 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 106 may contain a similar formulation but have 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 ratios of IVSS 106 in the delivery container 102. This ratio can vary between about 0.5% and about 12% of the final volume in the delivery container 102. Additionally, citrate salts may increase the risk of glass delamination when filled in glass vials. If citrate salts are necessary for the stabilization of the drug product (determined for each product), the delivery container 102 may be constructed from CZ or other plastic compositions. Other examples of components for the appropriate IVSS 106 are also possible.An appropriate IVSS106 concentration prevents protein-plastic interactions and / or surface adsorption at the lower limit of the concentration range that can potentially vary the effective amount, even with slight loss. The following table shows exemplary component concentrations for various IVSS concentrations.

[0047]

Table 2

[0048] By providing pre-filled IVSS106 within the delivery container 102, a separate container used to contain IVSS106 is no longer necessary, reducing the overall footprint of the system 100. Additionally, the need to prepare a needle and syringe assembly to inject IVSS106 into the delivery container, ensure that this prepared needle and syringe assembly is sterile, and / or ensure that the correct volume of IVSS is added to container 102 is eliminated.

[0049] Some conventional systems may provide a delivery container 102 overfilled with saline 108 when more saline 108 is provided to the delivery container than is required for the dosage. In these systems, it may be necessary to remove a certain amount of saline 108 prior to preparing the drug dosage, which may require preparing a sterile extraction tool (e.g., a needle and syringe assembly) and carefully extracting the correct amount of saline 108. Conversely, the disclosed system 100 further eliminates this process since the delivery container 102 is pre-filled with the required amount of saline 108. Additionally, the risk of needle sticks due to the transfer of IVSS106 into and / or saline 108 out of container 102 may be reduced or mitigated.

[0050] The pre-filled drug product vial or syringe 110 includes a vial body 111 defining an internal volume 112 and a vial adapter 114. The internal volume 112 may be sterile. In some approaches, the vial adapter 114 may also be a CSTD that fits, engages, and / or couples to the delivery container adapter 105. Similar to the pre-filled drug delivery container 102, the internal volume 112 of the pre-filled drug product vial 110 contains a predetermined amount of drug product or active pharmaceutical ingredient (“API”) 116 (e.g., from about 2 mcg to about 100 mcg), depending on the BiTE (registered trademark) and vial size, in a powder form (i.e., lyophilized form) that requires reconstitution in the illustrated example. In other examples, the drug product 116 may be in liquid form and may not require reconstitution. Nevertheless, since the system 100 contains the correct amount of drug product 116, there is no need to add additional amounts to the drug product 116 in a sterile environment. In some examples, the API may, optionally, be in the form of a half-life extended (“HLE”) BiTE (registered trademark) and / or a monoclonal antibody (“mAb”) for intravenous administration. These HLE BiTEs include an antibody Fc region that advantageously provides different drug properties such as a longer half-life and an extended half-life. Thus, such APIs may be preferred since they can maintain a 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.

[0051] The pre-filled reconstitution container 120 may be in the form of a similar container including a vial, a pre-filled syringe, or a reconstitution container body 121 defining an internal volume 122 and a reconstitution container adapter 124. The internal volume 122 may be sterile. In some techniques, the reconstitution container adapter 124 may also be a CSTD that fits, engages, and / or couples to the vial adapter 114 (or, in the example where the pre-filled reconstitution container 120 is in the form of a syringe, the container adapter 124 may be a needle). Similar to the pre-filled drug delivery container 102 and the pre-filled drug product vial 110, the pre-filled reconstitution container 120 contains a predetermined amount of diluent (e.g., water for injection without preservatives or “WFI”) 126 (e.g., from about 0.5 mL to about 10 mL) to be added to the pre-filled drug product vial 110 for reconstitution of the drug product 116. In some examples, WFI preserved with benzyl alcohol (or containing any other optional preservative) may be used.

[0052] More specifically, the drug product 116 is reconstituted prior to addition to the delivery container 102 by fitting the vial adapter 114 of the pre-filled drug product vial 110 to the reconstitution container adapter 124 of the pre-filled reconstitution container 120 and transferring the diluent 124 into the drug product vial 110 (see step 204 of FIG. 4). Next, the contents may be gently stirred, vortexed, and / or inverted to mix the components, thereby forming the desired mixture. The reconstituted drug product vial 110 may then be visually inspected to confirm for completeness and / or that proper mixing has occurred.

[0053] As previously described, in some examples, the pre-filled drug product vial 110 may be in the form of a pre-filled syringe containing the drug product 116. In these examples, the drug product 116 may be in the form of a liquid BiTE® formulation used in combination with a monoclonal antibody (mAb). In these examples, the drug product 116 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, when more conventional needle-syringe injection / delivery into the container 102 is preferred, and may be added directly to the delivery container 102 without using a vial adapter system (such as the CSTD described above). In these examples, the pre-filled drug product vial 110 may or may not need to be reconstituted prior to transfer of the drug product 116 to the delivery container 102.

[0054] The reconstituted drug contained within the pre-filled drug vial 110 may then be transferred into the drug delivery container 102 by fitting the vial adapter 114 of the pre-filled drug product vial 110 to the delivery container adapter 105 of the delivery container 102 (see step 206 in FIG. 4). As a result, this transfer of the reconstituted drug into the delivery container 102 can be performed quickly (thus significantly reducing the preparation time) and safely because there is no withdrawal assembly (e.g., a Luer lock needle and syringe mechanism). The systems described herein avoid and / or eliminate the possibility of needle sticks and / or leakage due to overpressure in the vial. Additionally, contamination is reduced due to the use of a closed drug transfer system, while conventional assemblies use components that are open to the environment and thus may be exposed to contamination.

[0055] The drug delivery system 100 may include any number of additional and / or optional features or alternative means. For example, any one or more of the delivery container adapter 105, the vial adapter 114, or the reconstitution container adapter 124 may be in the form of ports or coupling mechanisms respectively coupled to the pre-filled delivery container 102, the pre-filled drug product vial 110, and the reconstitution container 120. These ports may then be coupled to a CSTD device to enable flow between the desired containers. Thus, a CSTD device having appropriate coupling mechanism dimensions may be included in the system 100.

[0056] In the foregoing description, various devices, assemblies, components, subsystems, and methods related to drug delivery devices have been described. The devices, assemblies, components, subsystems, methods, or drug delivery devices can further include, or be used with, drugs including, but not limited to, the drugs specified below, as well as their generic and biosimilar equivalents. As used herein, the term drug can be used interchangeably with other similar terms and refers to any kind of agent or therapeutic material including traditional and non-traditional pharmaceuticals, nutraceuticals, supplements, biological agents, biologically active agents and compositions, macromolecules, biosimilars, biological equivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic pharmaceuticals. Non-therapeutic injectable materials are also included. The drug may be in liquid form, lyophilized form, or reconstituted from lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0057] The drug is contained within 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, a cartridge, or a pre-filled syringe.

[0058] 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).

[0059] In other embodiments, the drug delivery device may contain or be used with an erythropoiesis stimulating agent (ESA) formulation that can 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" means, for example, any protein that binds to a receptor and directly or indirectly causes activation of the erythropoietin receptor by causing receptor dimerization. Erythropoiesis stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis stimulating proteins include Epogen® (epoetin alpha), Aranesp® (darbepoetin alpha), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alpha), epoetin alpha Hexal, Abseamed® (epoetin alpha), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin, and their molecules or variants or analogs, but are not limited thereto.

[0060] 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 human monoclonal antibodies; Myostatin-binding proteins, peptibodies, related proteins, etc., including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., particularly those that inhibit activities mediated by binding to the receptors for IL-4 and / or IL-13; 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 humanized and fully human monoclonal antibodies, including but not limited to humanized and fully human antibodies such as human CD22-specific IgG antibodies, including, for example, dimers of human-mouse monoclonal hLL2γ chain disulfides bound to the human-mouse monoclonal hLL2κ chain, such as the human CD22-specific fully humanized antibody of epratuzumab (CAS Registry Number 501423-23-0); IGF-1 receptor-specific antibodies, peptibodies, and related proteins, etc., including but not limited to anti-IGF-1R antibodies; B7-related protein 1-specific antibodies, peptibodies, related proteins, etc. (also referred to as 「B7RP-1」, B7H2, ICOS-L, B7h, and CD275), including but not limited to fully human IgG2 monoclonal antibodies that bind to epitopes of the first immunoglobulin-like domain of B7RP-1, 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; IL-15-specific antibodies, peptibodies, related proteins, etc., including but not limited to HuMax IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies, such as 146B7, etc.; human IFNIFN-γ specific antibodies, peptibodies, related proteins, etc. including but not limited to 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 / SF: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 (registered trademark) (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex (registered trademark) (epoetin alfa), Erbitux (registered trademark) (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin (registered trademark) (somatropin, human growth hormone), Herceptin (registered trademark) (trastuzumab, anti-HER2 / neu (erbB2) receptor mAb), Humatrope (registered trademark) (somatropin, human growth hormone), Humira (registered trademark) (adalimumab), Vectibix (registered trademark) (panitumumab), Xgeva (registered trademark) (denosumab), Prolia (registered trademark) (denosumab), Enbrel (registered trademark) (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Nplate (registered trademark) (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution, Infergen (registered trademark) (interferon alfacon-1), Natrecor (registered trademark) (nesiritide, recombinant human B-type natriuretic peptide (hBNP)), Kineret (registered trademark) (anakinra), Leukine (registered trademark) (sargramostim, rhuGM-CSF), LymphoCide (registered trademark) (epratuzumab, anti-CD22 mAb), Benlysta (trademark) (lynphosphostat B, belimumab, anti-BlyS mAb), Metalyse (registered trademark) (tenecteplase, t-PA analog), Mircera (registered trademark) (methoxypolyethylene glycol-epoetin beta), Mylotarg (registered trademark) (gemtuzumab ozogamicin), Raptiva (registered trademark) (efalizumab), Cimzia (registered trademark) (certolizumab pegol, CDP 870), Soliris (trademark) (eculizumab), pexelizumab (anti-complement C5), Numax (registered trademark) (MEDI-524), Lucentis (registered trademark) (ranibizumab), Panorex (registered trademark) (17-1A, edrecolomab), Trabio (registered trademark) (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 US 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 (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb, and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin 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).

[0061] In some embodiments, the drug delivery device contains a sclerostin antibody such as, but not limited to, romosozumab, blosozumab, or BPS 804 (Novartis). In other embodiments, the drug delivery device may contain or be used with 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 with rilotumumab, vectibix, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be filled with IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including, but not limited to, OncoVEX GALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042, or the device may be used with these. In some embodiments, the drug delivery device may contain or be used with an endogenous tissue inhibitor of metalloproteinase (TIMP), such as, but not limited to, TIMP-3. Antagonistic antibodies to the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab and bispecific antibody molecules that target the CGRP receptor and other headache targets, may also be delivered using the drug delivery device of the present disclosure. In addition, bispecific T cell engager (BiTE®) antibodies, such as, but not limited to, half-life extended BiTEs that contain the antibody Fc region, BLINCYTO® (blinatumomab), can be used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may contain or be used with an APJ macromolecule agonist such as, but not limited to, apelin or an analog 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.

[0062] 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. Using either current technology or technology developed after the filing date of this patent, many alternative embodiments can be implemented, and such embodiments are still within the scope of the claims that define the invention disclosed herein.

[0063] 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. 1. A method of preparing a drug for delivery, comprising: Providing a diluent contained in a diluent container; Providing a drug product contained within a drug product container; fluidly connecting the diluent container and the drug product container; forcing at least a portion of the diluent from the diluent container into the drug product container with a pump to at least partially reconstitute the drug product. A method comprising:

2. The method of claim 1 further comprising the step of operating the pump.

3. 3. The method of claim 1 or 2, further comprising providing a volume of saline and a volume of intravenous stabilization solution ("IVSS") contained in a solution container.

4. 4. The method of claim 3, further comprising forcing at least a portion of the volume of saline and the volume of IVSS from the solution container into the drug product container by the pump.

5. 4. The method of claim 3, further comprising providing a valve configured to selectively fluidly connect one of the diluent container and the solution container to the drug product container.

6. configuring the valve to fluidly connect one of the diluent container and the solution container to the drug product container; forcing, by the pump, at least a portion of the diluent from the diluent container and one of the quantity of saline and the quantity of IVSS from the solution container into the drug product container; The method of claim 5 further comprising:

7. configuring the valve to fluidly connect the other of the diluent container and the solution container to the drug product container; forcing the at least a portion of the diluent from the diluent container and the other of the quantity of saline and the quantity of IVSS from the solution container into the drug product container by the pump; The method of claim 6 further comprising:

8. The method of any one of claims 5 to 7, wherein the valve includes a hydrophilic filter.

9. The method of any one of claims 1 to 8, wherein the diluent comprises water for injection ("WFI").

10. The method according to any one of claims 1 to 9, wherein the diluent container is a soft bag.

11. The method of any one of claims 1 to 10, wherein the drug product container is a soft bag.

12. The method according to any one of claims 1 to 11, wherein the solution container is a soft bag.

13. The method of any one of claims 1 to 12, further comprising the step of fluidly connecting the diluent container to the drug product container via a sterile connector.

14. The method of any one of claims 1 to 13, further comprising the step of fluidly connecting the solution container to the drug product container via a sterile connector.

15. The method of any one of claims 1 to 14, wherein the IVSS comprises a pretreatment surfactant or polysorbate 80.

16. The method of any one of claims 1 to 15, wherein the predetermined amount of diluent is from about 0.5 mL to about 10 mL.

17. The method of any one of claims 3 to 10, wherein the predetermined amount of saline is from about 50 mL to about 500 mL.

18. 12. The method of any one of claims 3 to 11, wherein the predetermined amount of IVSS is from about 1 mL to about 30 mL.

19. 19. The method of any one of claims 1 to 18, further comprising removing the drug product container and the diluent container from a common kit package.

20. 20. The method of any one of claims 1 to 19, wherein the drug product is in the form of a Bispecific T Cell Engager (BiTE®).

21. 3. The method of claim 2, wherein the BiTE is a half-life extended (HLE) BiTE.

22. 1. A drug delivery system comprising: A diluent container for containing a diluent; a drug product container for containing a drug product; at least one fluid pathway connector configured to at least selectively fluidly connect said diluent container and said drug product container; a pump operatively connected to the fluid pathway connector and configured to force at least a portion of the diluent from the diluent container into the drug product container to at least partially reconstitute the drug product. A drug delivery system comprising:

23. 23. The drug delivery system of claim 22, further comprising a solution container containing a predetermined amount of saline and a predetermined amount of intravenous stabilizing solution ("IVSS").

24. 24. The drug delivery system of claim 23, wherein the pump is configured to force the volume of saline and at least a portion of the volume of IVSS from the solution container into the drug product container.

25. 25. The drug delivery system of claim 23 or 24, wherein the at least one fluid pathway connector includes a valve configured to selectively fluidly connect one of the diluent container and the solution container to the drug product container.

26. 26. The drug delivery system of claim 25, wherein the valve includes a hydrophilic filter.

27. The drug delivery system of any one of claims 22 to 26, wherein the pump is a peristaltic pump.

28. The drug delivery system of any one of claims 22 to 27, wherein the diluent container, the drug product container and the pump are from a common kit package.

29. 30. The drug delivery system of claim 28, wherein the common kit package further comprises the solution container and the at least one fluid pathway connector.

30. 30. The drug delivery system of any one of claims 22 to 29, wherein the drug product is in the form of a Bispecific T Cell Engager (BiTE®).

31. 31. The drug delivery system of claim 30, wherein the BiTE is a half-life extended (HLE) BiTE.

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