Continuous dosing system and approach

Abstract

To provide an improved method and system for administration preparation and a delivery system.SOLUTION: A drug delivery system 100 includes: a delivery container 102 including a container body 103 adapted to accommodate a drug therein; a supply line 110; and a flow rate monitor 120. The delivery container further includes inlet and outlet ports and is constructed from a resilient material. The container body is adapted to exert an urging force on the drug to expel the drug from the outlet port. The supply line is operably coupled to the outlet port to deliver the drug to a user. The flow rate monitor is operably coupled to at least one of the delivery container and the supply line. The flow rate monitor includes a flow rate sensor that senses a flow rate of the drug within the supply line.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 804,506, filed February 12, 2019, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to drug delivery systems and methods, and more particularly, to improved techniques for dosage preparation and delivery systems. [Background technology]

[0003] Drugs are administered to treat a variety of conditions and diseases. Intravenous ("IV") therapy is a drug administration process that delivers drugs directly into a patient's veins using an infusion solution contained in a container (e.g., a soft bag). These processes may take place in a medical facility or, in some cases, at a remote location such as the patient's home. For home use, disposable IV pumps in the form of elastic balloons may be used to allow patients to administer their own medication. These take-home systems are generally non-programmable, come in a variety of volumes and flow rates, are lightweight during delivery, and do not require expensive maintenance and / or service infrastructure. However, these disposable systems often require the drug to remain within a specific flow rate range, but cannot alert the patient if the device is blocked or occluded. Compared to reusable systems, disposable systems generally do not rely on large, bulky electronics for proper operation; rather, these devices typically use inherent elasticity to generate drug delivery pressure, which, in combination with the resistance of the tubing, results in a predetermined drug flow rate. In contrast, reusable systems often have large power sources that allow for days of continuous use, and typically include user interfaces with multiple complex menus.

[0004] Often, medical personnel must prepare the drug by forcing the drug into the balloon using their own force to overcome the balloon's natural resistance, which can be difficult with drugs of various viscosities and / or when filling balloons with relatively high elasticity. Since these devices generally do not have programmable features, various factors can affect the accuracy of the drug flow rate. In addition, these elastic balloons may not be able to generate the necessary pressure near the end of the dosing cycle, and as a result, the patient may not receive the full intended dose.

[0005] As described in further detail below, the present disclosure describes systems and methods for patient monitoring and interventional dosing techniques that embody advantageous alternatives to existing systems and methods that may address one or more of the problems or needs referenced herein, as well as provide other benefits and advantages. Summary of the Invention [Means for solving the problem]

[0006] According to a first aspect, a drug delivery system includes a delivery container including a container body adapted to contain a drug therein, a supply line, and a flow monitor. The delivery container is made of a resilient material further including an inlet port and an outlet port. In some examples, the delivery container may take the form of a balloon. The container body is adapted to provide a biasing force to the drug to expel the drug from the outlet port. The supply line is operably coupled to the outlet port for delivering the drug to a user. In some examples, the supply line takes the form of a spiral tube. The flow monitor is operably coupled to at least one of the delivery container and the supply line. The flow monitor includes a flow sensor to sense a flow rate of the drug in the supply line.

[0007] In some examples, the flow monitor includes a fluid flow control device in fluid communication with the supply line and a controller operably coupled to the flow sensor and the fluid flow control device. The controller receives a sensed flow rate from the flow sensor and compares the sensed flow rate to a desired flow rate to calculate a difference value. When the difference value exceeds a threshold, the controller causes the fluid flow control device to adjust an operating parameter. In some examples, the fluid flow control device takes the form of a pump or a valve. In some forms, the operating parameter is at least one of a drive force and a valve position.

[0008] In some examples, the flow monitor further includes an alarm operably coupled to the controller. In these examples, the controller activates the alarm when the difference value exceeds an alarm value. The alarm value may be based at least in part on a risk profile of the drug contained in the delivery container. The flow monitor may additionally include an interface coupled to the controller to receive the at least one input, and a display coupled to the controller. Furthermore, in some examples, the drug delivery system may include a fluid pathway compliance member disposed downstream of the flow monitor.

[0009] According to another aspect, a flow monitor for a take-home medication delivery system includes a coupling mechanism for coupling to a portion of the medication delivery system, a supply line operably coupled to the coupling mechanism, a flow sensor in fluid communication with the supply line, a fluid flow control device in fluid communication with the supply line, and a controller operably coupled to the flow sensor and the fluid flow control device. The flow sensor senses a flow rate of the medication in the supply line. The controller receives an input value indicative of a desired one of a plurality of medications to be administered and additionally receives a sensed flow rate from the flow sensor, compares the sensed flow rate to a risk profile, and calculates a difference value. When the difference value exceeds a threshold, the controller causes the fluid flow control device to adjust an operating parameter of the medication delivery system.

[0010] The above needs are met, at least in part, by the provision of continuous medication administration systems and techniques as described in the following detailed description, particularly when considered in conjunction with the drawings. [Brief description of the drawings]

[0011] [Figure 1] 1 illustrates an exemplary take-home disposable drug delivery system, according to various embodiments. [Diagram 2] 2 illustrates an exemplary flow monitor of the exemplary take-home disposable drug delivery system of FIG. 1, in accordance with various embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Those skilled in the art will appreciate that the elements in the figures are depicted 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 improve understanding of the various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to not overly distract from the illustrations of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular occupying order, although those skilled in the art will appreciate that such specificity with respect to order is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meanings, as set forth above, that would be given to such terms and expressions by those skilled in the art, unless a different specific meaning is explained herein.

[0013] Referring to the figures, a disposable, take-home drug delivery system 100 is presented in accordance with these various embodiments. Drug delivery systems differ from electromechanical programmable IV pumps in that systems such as the drug delivery system 100 described herein rely primarily and / or in part on the pump's material properties (rather than an external power source) to administer drugs to a patient. These take-home systems described herein are generally smaller, lower cost, and easier to use than electromechanical programmable IV pumps, and as a result may be used in settings other than medical facilities (e.g., the patient's home, office, and / or elsewhere). The focus on a single therapy or group of therapies may result in a simpler approach to user interface and risk assessment, which may reduce cost of goods sold ("COGS"), power requirements, and size, which may in turn increase value to the patient. The system 100 includes small, energy-efficient "add-on" units that may be incorporated into the take-home pump system with minimal complexity. The system 100 may be used in intravenous, subcutaneous, intraarterial, intramuscular, and / or epidural delivery techniques with delivery times ranging from about 5 minutes to about 8 hours. Use of the drug delivery system 100 described herein reduces patient anxiety and confusion due to the use of positive pressure flow, which does not require regulatory guidance for air bubble detection, as compared to peristaltic pump mechanisms. The system described herein provides an optional, single-use, pre-programmed add-on unit that provides limited functionality at the patient level, thus simplifying the add-on system.

[0014] The system 100 includes a drug delivery container 102 (e.g., an intravenous drug delivery container), which may also be considered a medication reservoir, comprising a container body 103 having an interior volume 104 that contains a drug 101 therein. The interior volume 104 may be sterile. The container 102 may be an off-the-shelf disposable elastomeric pump of any desired size. In the illustrated example, the delivery container 102 also functions as a drive mechanism for administering the drug 101 to the patient.

[0015] Specifically, the container body 103 may be made of elastic and / or resilient materials. Generally speaking, the container body 103 is in a relaxed state before being filled with the drug 101 therein, and when the drug 101 is inserted into the container body 103, the container body 103 expands or stretches outward, increasing the internal volume 104. The elasticity of the container body 103 creates a contraction force on the internal volume 104, which ultimately acts on the drug 101 for drug administration. The container 102 further includes an inlet fill port or mechanism 106 and an outlet port or mechanism 108. These ports 106, 108 can be any type of port that allows for selective coupling of drug containers, vials, syringes, and the like. In some examples, the inlet fill port 106 and the outlet fill port 108 may include a valve or seal mechanism to selectively allow fluid to flow through and may be capped to prevent outside contamination. Coupled to the outlet port 108 is an IV pump supply line or tubing 110 that is operably coupled to the outlet fill port 108 and sized to accommodate the flow of medication 101 for administration to a patient. This IV supply line 110 may be prefabricated and may have any number of desired characteristics, such as length and / or flexibility. Any number of additional components may be coupled to the IV supply line 110, such as clips, clamps, filters (e.g., air removal filters), etc.

[0016] Typically, a healthcare professional (e.g., a clinical pharmacy) will stock a variety of delivery containers 102, thereby providing ready access to the reservoirs and drives (i.e., motive power). One exemplary brand of delivery container 102 is the Easy Pump (e.g., Easy Pump LT 125-5-S, LT 279-27-S, etc.), which may include internal volumes that vary from about 15 ml to about 500 ml. These models may come in high, medium, low, and / or extra-low flow configurations, resulting in a wide variety of desired drug flow rates (e.g., from about 0.3 ml / day to about 500 ml / hour). As a result, nominal infusion times may vary between about 5 minutes to about 60 hours, depending on the desired usage.

[0017] The system 100 additionally includes a flow monitor 120 that may be operably coupled to the IV supply line 110. In some examples, the flow monitor 120 may be directly coupled to the outlet port 108. The flow monitor 120 may include a flow sensor 126 that senses the flow rate of the drug 101 in the IV supply line 110. More specifically, as shown in FIG. 2 , the flow monitor 120 includes a controller 122, a power source 124, the above-mentioned flow sensor 126 operably coupled to the controller 122, and a fluid flow control device 128 operably coupled to the controller and in fluid communication with the IV supply line 110. The flow monitor 120 may additionally include any number of optional components, such as, for example, an interface 130 and an alarm 132.

[0018] The flow monitor 120 may be provided in the drug delivery system 100 packaging to facilitate its use (although its use is not required if the medical practitioner strongly advocates against its use). In other words, the flow monitor 120 may be an optional component in the take-home drug delivery system 100 that the medical practitioner and / or the patient may use as they deem appropriate. The flow monitor 120 may take the form of a clamshell housing that houses each of the components therein, may include an inlet 120a and an outlet 120b, and may include an inner tube 121 extending between the inlet 120a and the outlet 120b. In some examples, the IV supply line 110 is coupled to the inlet 120a, and a second supply line 110' (which is ultimately coupled to the user for drug administration) is coupled to the outlet 120b. One exemplary flow monitor 120 is provided by Sensirion (e.g., Sensirion LD20-0600L single use liquid flow sensor). Another such example is the DripAssist Infusion Rate Monitor, available at www.boundtree.com. Other examples are possible.

[0019] The flow monitor 120 differs from complex electromechanical infusion pumps in that it lacks user / patient programmability. Specifically, the flow monitor 120 is "programmed" at a location upstream from the user's home environment (e.g., at a pharmacy prior to issuing a prescription to the patient). In this sense, the flow monitor 120 can be considered a single-use, fixed-program, pre-programmed device that provides only a limited set of functions to the patient (e.g., starting or pausing administration). Furthermore, compared to complex electromechanical IV pump systems, the flow monitor 120 described herein also lacks typical programmable functions provided to a medical practitioner. In some instances, the "programmability" provided to a medical practitioner may be limited to simply inputting prescribed drug and / or dosage information. Thus, in some instances, the flow monitor 120 may not be reprogrammable after the initial programming.

[0020] The controller 122 includes software 122a adapted to control its operation, any number of hardware elements 122b (e.g., non-transitory memory modules and / or processors, etc.), any number of inputs, any number of outputs, and any number of connections. The software 122a may be loaded directly into a non-transitory memory module of the controller 122 in the form of a non-transitory computer readable medium, or may be located remotely from the controller 122 and communicate with the controller 122 via any number of control techniques. The software 122a includes executable program instructions that may include logic, commands, and / or logic and / or commands for controlling the flow monitor 120. The software 122a may or may not include an operating system, an operating environment, an application environment, and / or a user interface 130.

[0021] The power source 124 can be any type of power source capable of powering the components of the flow monitor 120. For example, the power source 124 can take the form of a watch or a cell battery sized to power the flow monitor 120 for an entire administration cycle. Other examples are possible. The flow sensor 126 can be any type of flow sensor (e.g., the examples above) and can include a sensor inlet 126a and a sensor outlet 126b that couple to the inner tube 121 through which the medication 101 passes during administration. Upon sensing the measured flow rate, the flow sensor 126 transmits this data to the controller 122.

[0022] The fluid flow control device 128 can be any type of device capable of modifying the fluid flow rate of the drug 101. In some examples, the fluid flow control device 128 can be any type of valve mechanism, and in other examples, the fluid flow control device 128 can be any type of pump mechanism. The fluid flow control device 128 includes a flow control device inlet 128a and an outlet 128b that couple to the inner tube 121 through which the drug 101 passes during administration. In other words, the fluid flow control device 128 is disposed within the flow path of the drug 101. The fluid flow control device 128 includes at least one operating parameter that can be modified during operation of the flow monitor 120. In some examples, the operating parameter can be a drive or power output (e.g., a force or power provided by a pump or motor) or a valve position. Other examples are possible.

[0023] When the controller 122 receives input values ​​(e.g., from the user interface 130, described below) indicating a desired drug and / or dosage to be administered, the controller 122 initiates a risk profile corresponding to the selected drug. This risk profile may include an indication of an acceptable flow rate range for the particular drug 101 to be administered, and / or additional important operational values ​​associated with the drug. The controller 122 receives the sensed flow rate from the flow sensor 126 and compares this value to the data contained in the risk profile (e.g., a required flow rate value or range of values) to generate or calculate a difference value. If the difference value exceeds a threshold value (e.g., within about 5% of the desired flow rate or flow rate range), the controller 122 sends a signal to the fluid flow control device 128 to adjust an operational parameter, thereby modifying the fluid flow rate of the drug 101. In some instances, it may be desirable to have the flow rate of the fluid flow control device 128 be between the average flow rate and the full scale of the flow sensor 126.

[0024] The user interface 130 may include several inputs (e.g., buttons) and / or displays that allow a medical practitioner and / or patient to initially configure the flow monitor 120. Typically, the interface 130 includes a limited number of patient-level settings and inputs to reduce user confusion. For example, a medical practitioner may use the interface 130 to input a desired flow rate, duration of drug delivery, and / or risk profile of the particular drug 101 to be administered, which one or more inputs are transmitted to the controller 122. In some examples, all or part of this information may already be stored in the controller 122, such that the medical practitioner need only input the drug name and / or dosage. As described above, the software 122a on the controller 122 may determine the desired output values ​​required to operate the flow monitor 120 based on one or more inputs received from the interface 130, and may determine the required tolerances (e.g., thresholds and / or alarm values). Stated another way, the interface 130 may be configured only to generate an output and may not receive any input beyond selecting the desired drug.

[0025] The interface 130 may additionally include buttons to start and / or pause operation of the system 100 so that a user can begin drug administration at a desired time. The interface 130 may also include a display that can indicate desired and / or actual flow rate values, error messages, remaining administration time, etc. In some examples, the interface may be located on or within the flow monitor 120, or may possibly be implemented via an external connection (e.g., via a portable electronic device such as a smartphone, computer, tablet, etc.).

[0026] The optional alarm 132 can act as a feedback device to alert the user to potential problems in the system 100 (e.g., complete and / or partial occlusion). The alarm can take the form of a speaker that makes an audible noise, a vibrating buzzer, and / or a flashing light. Other examples are possible. In these examples, once the user inputs settings (e.g., particular drug, desired flow rate, etc.) into the interface 130, the controller 122, via the software 122a, can determine an appropriate risk profile that may include an alarm value. If the sensed flow rate value obtained from the sensor 126 exceeds this alarm value, the controller 122 can send a signal to trigger and / or activate the alarm 132. For example, the alarm value can be in the range of about 10-15% from the desired flow rate. In other words, if the measured or sensed flow rate is higher or lower than 10%-15% of the desired flow rate, an alarm can be triggered to alert the user to take appropriate action. Advantageously, the use of the alarm 132 avoids the patient having to restart a new delivery cycle upon the occurrence of an occlusion.

[0027] In some examples, the system 100 may additionally include at least one compliance member in the form of a flexible tube, diaphragm, and / or bellows that predictably absorbs high frequency fluid displacement motion. In some drug delivery systems that operate at high frequencies (e.g., with a duty cycle of more than 50% or with the chamber filled for at least 50% of the time), a compliance member may be necessary to ensure delivery accuracy. Delivery at low frequencies may allow sufficient time for "leveling out" and predictable delivery, but at high frequencies (e.g., with components such as rigid flow controller systems), accuracy may be reduced (e.g., compliance) after the system is fully primed to eliminate air bubbles. Placing a compliance member downstream of the flow monitor ensures delivery accuracy.

[0028] So configured, the flow monitor 120 may be implemented as an optional component of an existing delivery system 100 for use in a variety of locations, including a patient's home, office, or other non-medical facility environment. In some examples, the flow monitor 120 may be water resistant or waterproof so that the user can use it while bathing. The flow monitor 120 may be provided on a coiled second supply line 110' that automatically retracts out of the way of the user.

[0029] Advantageously, the flow monitor 120 provides increased accuracy compared to conventional reusable systems (e.g., conventional systems have an accuracy of about ±15%, while the systems described herein may provide an accuracy of about ±6%), which may reduce and / or eliminate patient concerns regarding remaining amount of medication 101. The flow monitor 120 may allow for a constant pressure to be delivered for a longer period of time. Additionally, there is no need to overfill the container 102, as less medication is wasted and feedback is provided in the event of a blockage. Advantageously, alarms may be minimized by using custom risk profiles based on the particular medication 101.

[0030] The flow monitor 120 may also be replaced at each refill, so the battery 124 does not need to occupy a large volume. Thus, the flow monitor 120 may have a small, unobtrusive, patient-friendly size that is easy to carry and suitable for pain management. In some examples, a relatively high flow rate efflux pump may be combined with the flow monitor 120 to provide a low duty cycle that allows flow for only about 6% of the total administration time, thereby reducing the time that the sensor 126 needs to be powered. Most drug delivery cycles may be time averaged such that the flow monitor 120 delivers multiple high flow rates in a short period of time, which clinically equates to a constant low flow rate.

[0031] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used with drugs, including but not limited to the drugs identified below, and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may be used to refer to any type of pharmaceutical or therapeutic material, including 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 included. 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.

[0032] The drug is contained within a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the drug for treatment. The primary container may be a vial, cartridge, or pre-filled syringe.

[0033] In some embodiments, the reservoir of the drug delivery device may be loaded with or the device may be used with colony stimulating factors such as granulocyte colony stimulating factor (G-CSF). 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).

[0034] In other embodiments, the drug delivery device may contain or be used with an erythropoietin stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoietin. In some embodiments, an ESA is an erythropoietin stimulating protein. As used herein, "erythropoietin 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. Erythropoietin 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. Erythropoietin stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), Epoetin 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.

[0035] 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 in particular inhibit activities mediated by binding of IL-4 and / or IL-13 to its receptor; 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-linked to human-mouse monoclonal hLL2 kappa chain, e.g., human C dimers of epratuzumab (CAS Registry No. 501423-23-0). human CD22-specific antibodies, including but not limited to, humanized and fully human antibodies, including but not limited to, humanized and fully human monoclonal antibodies, including but not limited to, human CD22-specific IgG antibodies, particularly including but not limited to, fully humanized antibodies specific for D22; 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, fully human IgG2 monoclonal antibodies specific for B7RP-1 (also referred to as "B7RP-1", B7H2, ICOSL, B7h, and CD275), including but not limited to, a fully human IgG2 monoclonal antibody that binds to an epitope in the first immunoglobulin-like domain of B7RP-1; HuMaxIL-15 specific antibodies, peptibodies, related proteins, etc., including but not limited to IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies; IFNγ specific antibodies, peptibodies, related proteins, etc., including but not limited to human IFNγ specific antibodies, and including but not limited to fully human anti-IFNγ antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., as well as other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptors. ("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, related proteins, etc. 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 beta-1a), Bexxar® (Tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (Interferon-beta), Campath® (Alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (Epoetin delta), Velcade® (Bortezomib), MLN0002 (Anti-α4β7mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Vectibix® (panitumumab), Xgeva (denosumab), Prolia® (denosumab), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCimhR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP IIb / IIia receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20 mAb), Tarceva® (erlotinib), Roferon-A® (interferon alpha-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-alpha4 integrin mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (VEGFR1 Ig domain fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (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-Clostridium difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβmAb(GC-1008), TRAIL-2 mAb (HGS-ETR2), TWEAK mAb, VEGFR / Flt-1 mAb, ZP3 mAb (HuMax-ZP3)

[0036] 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 BPS804 (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. Antagonist 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 device of the present disclosure. Additionally, bispecific T cell engaging (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), may be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery devices may contain or be used 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 device of the present disclosure.

[0037] The drug delivery devices, assemblies, components, subsystems, and methods have been described in terms of exemplary embodiments, but are not limited thereto. The detailed description should be construed as merely exemplary and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments still fall within the scope of the claims that define the invention disclosed herein.

[0038] Those skilled in the art will understand that numerous modifications, alterations, and combinations can be made to the above-described embodiments without departing from the spirit and scope of the invention disclosed herein, and such modifications, alterations, and combinations are to be construed as falling within the scope of the inventive concept.

Claims

1. a delivery container including a container body adapted to contain a drug therein, an inlet port, and an outlet port, the container body being made of a resilient material such that the container body is adapted to apply a biasing force to the drug to expel the drug from the outlet port; a supply line operably coupled to the outlet port for delivering the medication to a user; a flow monitor operably coupled to at least one of the delivery container and the supply line, the flow monitor including a flow sensor for sensing a flow rate of the drug in the supply line; A drug delivery system comprising:

2. The flow monitor, a fluid flow control device in fluid communication with the supply line; a controller operably coupled to the flow sensor and the fluid flow control device, a controller configured to receive the sensed flow rate from the flow sensor and compare the sensed flow rate to a desired flow rate to calculate a difference value, and when the difference value exceeds a threshold, the controller causes the fluid flow control device to adjust an operating parameter; The drug delivery system of claim 1 , comprising:

3. The drug delivery system of claim 2 , wherein the fluid flow control device comprises at least one of a pump and a valve.

4. 4. The drug delivery system of claim 3, wherein the operating parameter is at least one of power output and valve position.

5. A drug delivery system according to any one of claims 2 to 4, wherein the flow monitor further comprises an alarm operably coupled to the controller, the controller being configured to activate the alarm when the difference value exceeds an alarm value.

6. The drug delivery system of claim 5 , wherein the alarm value is based at least in part on a risk profile of the drug contained in the delivery container.

7. 7. The drug delivery system of claim 2, wherein the flow monitor further comprises: 1) an interface coupled to the controller for receiving at least one input; and 2) a display coupled to the controller.

8. The drug delivery system of any one of claims 1 to 7, further comprising a fluid path compliance member downstream of the flow monitor.

9. The drug delivery system of any one of claims 1 to 8, wherein the supply line comprises a spiral tubing member.

10. The drug delivery system of any one of claims 1 to 9, wherein the delivery reservoir comprises a balloon.

11. 1. A flow monitor for a drug delivery system, the flow monitor comprising: a coupling mechanism adapted to couple to a portion of the drug delivery system; a supply line operably coupled to the coupling mechanism; a flow sensor in fluid communication with the supply line, the flow sensor adapted to sense a flow rate of a drug in the supply line; a fluid flow control device in fluid communication with the supply line; a controller operably coupled to the flow sensor and the fluid flow control device, the controller including at least one risk profile for each of a plurality of drugs; The controller: receiving an input indicating a desired one of the plurality of medications to be administered; initiating said at least one risk profile for said desired one of said plurality of drugs; receiving the sensed flow rate from the flow sensor and comparing the sensed flow rate with the risk profile to calculate a difference value; When the difference value exceeds a threshold, causing the fluid flow control device to adjust an operating parameter of the drug delivery system. The controller and A flow monitor comprising:

12. The flow monitor of claim 11 , wherein the operating parameter is at least one of an actuation force and a valve position.

13. 13. The flow monitor of claim 11 or 12, wherein the flow monitor further comprises an alarm operatively coupled to the controller, the controller being adapted to activate the alarm when the difference value exceeds an alarm value.

14. The flow monitor of claim 13 , wherein the alarm value is based at least in part on the risk profile of the drug contained in the delivery container.

15. The flow monitor of any one of claims 11 to 14, wherein the fluid flow control device comprises at least one of a pump and a valve.

16. 16. The flow monitor of any one of claims 11 to 15, further comprising: 1) an interface coupled to the controller for receiving at least one input; and 2) a display coupled to the controller.

17. A flow monitor according to any one of claims 11 to 16, wherein the supply line comprises a spiral tubing member.

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