CONTINUOUS DOSING SYSTEMS AND APPROACHES

A drug delivery system includes a delivery container including a container body adapted to accommodate a drug therein, a supply line, and a flow rate monitor. The delivery container further includes inlet and outlet ports and is constructed from a resilient material that exerts 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 or the supply line and includes a digital controller, a fluid valve operably coupled to the digital controller, and a translating syringe in fluid communication with the fluid valve and operably coupled to the digital controller. The fluid valve, the translating piston, and the digital controller cooperate to regulate a flow rate of the drug.

FIELD OF DISCLOSURE

The present disclosure generally relates to drug delivery systems and methods. More particularly, the present disclosure relates to improved approaches for preparing and delivering dosing systems.

BACKGROUND

Drugs are administered to treat a variety of conditions and diseases. Intravenous (“IV”) therapy is a drug dosing process that delivers drugs directly into a patient's vein using an infusion contained in a container (e.g., a pliable bag). These processes may be performed in a healthcare facility, or in some instances, at remote locations such as a patient's home. A disposable IV pump in the form of an elasticized balloon may be used in an at-home setting to provide patients the ability to administer their own dosages. These take-home systems typically lack programming, are offered in a range of volumes and flow rates, and get lighter throughout delivery without the need for expensive maintenance and/or service infrastructure. However, oftentimes drugs in these disposable systems need to stay within a specific flow rate window, but they cannot alert a patient if the device becomes blocked or otherwise occluded. Compared to reusable systems, disposable systems generally do not rely on large, bulky electronics for proper operation, rather, these devices typically use their inherent elasticity to create a drug delivery pressure that, combined with tubing resistance, results in a predetermined drug flow rate. Conversely, reusable systems oftentimes have large power supplies that enable continued use for multiple days, and typically include a user interface having multiple, complex menus. In some examples, flow rate monitors may be used to monitor and adjust fluid flow of the drug. However, these systems are typically power-hungry and can have undesirable fluid pressure accuracies during varying stages of the drug administration process.

As described in more detail below, the present disclosure sets forth systems and methods for dosing techniques embodying advantageous alternatives to existing systems and methods, and that may address one or more of the challenges or needs mentioned herein, as well as provide other benefits and advantages.

SUMMARY

In accordance with a first aspect, a drug delivery system includes a delivery container including a container body adapted to accommodate a drug therein, a supply line, and a flow rate monitor. The delivery container further includes inlet and outlet ports and is constructed from a resilient material that exerts 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 or the supply line and includes a digital controller, a fluid valve operably coupled to the digital controller, and a translating syringe in fluid communication with the fluid valve and operably coupled to the digital controller. The fluid valve, the translating piston, and the digital controller cooperate to regulate a flow rate of the drug. In some examples, the flow rate monitor may be at least partially disposed within the container body.

In some examples, the digital controller causes the fluid flow control device to actuate the fluid valve or valves. The fluid valve may be in the form of a magnetically latching three-way valve that includes a valve inlet, a first valve outlet, and a second valve outlet. The translating syringe may include a cylinder defining a cylinder inlet and an internal volume. The cylinder inlet is in fluid communication with the first valve outlet of the fluid valve. The translating syringe further includes a piston disposed within the internal volume of the cylinder. In some examples, at least one end of travel sensor is provided that senses at least one directional limit of the piston.

In some approaches, the flow rate monitor may further include an interface coupled to the digital controller to receive at least one input and a display coupled to the digital controller. Further, the system may include an alarm operably coupled to the digital controller, an air trap, a filter, a flow restrictor, and/or a fluid path compliance member disposed downstream of the flow rate monitor.

In accordance with a second aspect, a drug delivery system includes a delivery container including a container body adapted to accommodate a drug therein, a supply line, and a flow rate monitor disposed within the container body. The delivery container further includes inlet and outlet ports and is constructed from a resilient material that exerts 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 includes a digital controller, a fluid valve operably coupled to the digital controller, and a translating syringe in fluid communication with the fluid valve and operably coupled to the digital controller. The fluid valve, the translating piston, and the digital controller cooperate to regulate a flow rate of the drug.

In accordance with a third aspect, a drug delivery system includes a delivery container including a container body adapted to accommodate a drug therein, a supply line, and a flow rate monitor. The delivery container further includes inlet and outlet ports and receives a driving force that causes the container body 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 or the supply line and includes a digital controller, a fluid valve operably coupled to the digital controller, and a translating syringe in fluid communication with the fluid valve and operably coupled to the digital controller. The fluid valve, the translating piston, and the digital controller cooperate to regulate a flow rate of the drug.

DETAILED DESCRIPTION

Turning to the figures, pursuant to these various embodiments, a disposable, take-home drug delivery system100is provided. The drug delivery system varies from an electromechanical programmable IV pump in that the systems such as the drug delivery system100described herein relies primarily and/or partially on material characteristics of the pump (as opposed to an external power source) to administer a drug to a patient. These take-home systems described herein are typically smaller, lower cost, and easier to use compared to electromechanical programmable IV pumps, and as a result, can be used in settings outside of a healthcare facility (e.g., at a patient's home, office, and/or other location). By focusing on a single therapeutic or class of therapeutics, a simpler approach to a user interface and risk assessment may be afforded, thereby potentially reducing costs of goods sold (“COGS”), power requirements, and size, thus increasing value to patients. The system100includes a small, energy efficient “add-on” unit that may be incorporated into a take-home pump system with minimal complexity. The system100may be used in intravenous, subcutaneous, intra-arterial, intramuscular, and/or epidural delivery approaches having delivery times between approximately five minutes and upwards of approximately 72 hours. By using the drug delivery system100described herein, patient anxiety and confusion is reduced due to the use of a positive pressure flow that eliminates the need for regulatory guidance for air bubble detection as compared to peristaltic pump mechanisms. The systems described herein provide an optional, single use, pre-programmed add-on unit that provides limited functionality at the patient level. Accordingly, the add-on system is simplified.

The system100includes a drug delivery container102(e.g., an intravenous drug delivery container) which could also be considered a medication reservoir that includes a container body103having an inner volume104that accommodates a drug101therein. In the illustrated example, the system100further includes a container105that surrounds the drug delivery container102for safety and other purposes. In some examples, the container105may be rigid. The inner volume104may be sterile. This container102may be an off-the shelf disposable elastomeric pump of any desired size. In the illustrated example, the delivery container102also functions as the drive mechanism that causes the drug101to be administered to the patient.

Specifically, the container body103may be constructed from an elastic and/or resilient material. Generally speaking, the container body103is in a relaxed state prior to filling the drug101therein, and upon inserting the drug101into the container body103, the container body103is expanded or stretched outwardly, and the inner volume104increases. The elasticity of the container body103generates a contraction force on the inner volume104that ultimately is exerted on the drug101for drug administration. In some examples, the container body103may be resilient or non-resilient, but may receive a driving force exerted thereon that in turn causes the container body103to exert an urging force on the drug101for drug administration. In these examples, the driving force may come from a spring member. In other examples, the driving force may be generated by a non-resilient surface that translates generally linearly in a cylinder under pressure from a spring or other resilient member.

The container102further includes an inlet fill port or mechanism106and an outlet port or mechanism108. These ports106,108may be of any type to allow for selective coupling of drug containers, vials, syringes, and the like. In some examples, the inlet fill port106and the outlet fill port108may include a valve or sealing mechanism to selectively permit fluid flow, and may be capped to prevent external contamination. Coupled to the outlet port108is an IV pump supply line or tubing110that is operably coupled to the outlet fill port108and dimensioned to accommodate flow of the drug101for patient administration (for example, via IV needle118). This IV supply line110may be an off the shelf item 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 line110such as, for example, clamps112, clips, filters (e.g., air elimination filters or traps114), flow restrictors116and the like.

Typically, healthcare professionals (e.g., clinical pharmacies) stock a variety of delivery containers102, thereby enabling ready access to the reservoir and drive (i.e., the motive force). One such example brand of delivery containers102is Easy Pump (e.g., Easy Pump LT 125-5-S, LT 279-27-S, etc.) which may include inner volumes104varying from approximately 15 mL to approximately 500 mL. These models may be in the form of high flow, medium flow, low flow, and/or ultra-low flow, and may result in a wide array of desired drug flow rates (e.g., between approximately 0.3 mL/day and approximately 500 mL/hour). As a result, a nominal infusion time may vary between approximately 5 minutes and upwards of approximately 72 hours depending on the desired usage.

The system100additionally includes a flow rate monitor120(i.e., a flow rate digital controller) that may be operably coupled to the IV supply line110. In some examples, the flow rate monitor120may be directly coupled to the outlet port108. In other examples, and as illustrated inFIG. 9, the flow rate monitor120may be disposed within the inner volume104of the drug delivery container102, and is configured to be positioned in a generally vertical arrangement when the system100is in use. The flow rate monitor120may include a digital controller122, a power source124, a fluid valve126operably coupled to the digital controller122, and a translating syringe128operably coupled to the digital controller122and in fluid communication with the IV supply line110. The flow rate monitor120may additionally include any number of optional components such as, for example, an interface130, an alarm132, and a filter134(e.g., a 35 micron filter positioned upstream of the valve126).

The flow rate monitor120may be provided with the drug delivery system100packaging to encourage its use (though its use is not required in the event a healthcare professional has strong preferences opposing its use). In other words, the flow rate monitor120may be an optional component in the take-home drug delivery system100that the healthcare professional and/or the patient may use as they deem appropriate. The flow rate monitor120may be in the form of a housing that accommodates each of the components therein, and may include an inlet port120aand an outlet120b,each of which may include any number and/or types of connecting ports, and may include internal tubing121(or, in some examples, an internal flow channel) extending between the inlet120aand the outlet120b.

The flow rate monitor120differs from complex electromechanical infusion pumps by lacking user/patient programmability. Specifically, the flow rate monitor120is “programmed” at a location that is upstream from the user's at-home environment (e.g., at a pharmacy prior to providing the patient with their prescription). In this sense, the flow rate monitor120may be viewed as a single-use, fixed programmed, pre-grammed or pre-programmed device that only provides the patient with a limited feature set (e.g., initiate or pause dosages). Further, compared to complex electromechanical IV pumping systems, the flow rate monitor120described herein additionally lacks the typical programmable features afforded to healthcare professionals. In some examples, the “programmability” afforded to healthcare professionals may be limited to simply inputting the prescribed drug and/or dosage information. Accordingly, in some examples, the flow rate monitor120may not be reprogrammable after an initial programming.

The digital controller122includes software122aadapted to control its operation, any number of hardware elements122b(such as, for example, a non-transitory memory module and/or processors), any number of inputs, any number of outputs, and any number of connections. The software122amay be loaded directly onto a non-transitory memory module of the digital controller122in the form of a non-transitory computer readable medium, or may alternatively be located remotely from the digital controller122and be in communication with the digital controller122via any number of controlling approaches. The software122aincludes logic, commands, and/or executable program instructions which may contain logic and/or commands for controlling the flow rate monitor120. The software122amay or may not include an operating system, an operating environment, an application environment, and/or the user interface130. Generally, the digital controller is adapted to cause the flow rate monitor to actuate the fluid valve or valves. The valve or valves may be solenoid driven, shape memory wire (e.g., muscle wire) driven, and/or motor driven. Other examples are possible.

The power source124may be any type of power source capable of powering the components in the flow rate monitor120. For example, the power source124may be in the form of a single or multi-cell battery commonly used in a wrist watch dimensioned to power the flow rate monitor120during a complete administration cycle. In one example, 250 ml of drug101may be delivered over a period of four days with a bolus interval of 45 minutes. Accordingly 128 doses of bolus will be administered at a rate of 1.953 ml per bolus. The flow rate monitor120may require a sensor power of 23 mAh, and a valve power of 0.7 mAh. Accordingly, a power source124capable of providing 75 mWh may be used. Other examples are possible.

The fluid valve126may be a magnetically latching three-way valve that includes a valve inlet126a,a first valve outlet126b,and a second valve outlet126c.The first valve outlet126selectively (e.g., via the digital controller122) couples to one of the valve inlet126aor the second valve outlet126cduring operation. Generally, such operation allows the translating syringe128to fill with drug101via the delivery container102, and expel the drug out the outlet120bof the flow rate monitor120.

The translating syringe128includes a cylinder136defining a cylinder inlet136aand an internal volume136b.The cylinder inlet136ais in fluid communication with the first valve outlet126bof the fluid valve126. In some examples, the cylinder136is dimensioned to have a throw sized for the desired bolus delivery (e.g., for 1.95 mL deliveries). The translating syringe128further includes a piston138disposed within the internal volume136bof the cylinder136. The translating syringe128may further include a spring140operably coupled to the piston138that urges the piston138in a direction towards the cylinder inlet136a.The translating syringe128additionally includes a stop142that limits travel in a direction away from the cylinder inlet136a(thereby resulting in a desired “throw distance”), and further includes at least one end of travel sensor144that senses when the piston138has reached its end of travel. In the illustrated example, two end of travel sensors144are used to determine both when the piston138is positioned at or near the cylinder inlet136aand when the piston138is positioned at or near the end of the throw distance. This sensed information is sent to the digital controller122.

In some examples, the spring force of the spring140, combined with the frictional force of the piston138must be less than a minimum urging force (e.g., the pressure) exerted on the drug101by the container body103. Accordingly, when the valve inlet126ais coupled to the first valve outlet126b,the drug101may enter into the internal volume136bof the cylinder136to fill the internal volume136buntil the piston138reaches the end of travel sensor144. Upon the end of travel sensor144transmitting the signal to the digital controller122, the digital controller122may transmit a control signal to the f126that actuates the fluid valve126(e.g., causes the fluid valve126to “switch” to a configuration where the first valve outlet126bis fluidly coupled to the second valve outlet126c). In other words, the first valve outlet126bmay act as a valve inlet, receiving the drug101contained within the internal volume136bof the cylinder136and allowing the drug101to flow through the second valve outlet126c.In this configuration, the spring140urges the piston138towards the cylinder inlet136a,thus expelling the drug101.

When the piston138reaches its end of travel and is positioned at or near the cylinder inlet136a,the end of travel sensor144positioned at or near the cylinder inlet136amay transmit a signal to the digital controller122that causes the digital controller122to again actuate the fluid valve126by placing the valve inlet126ain fluid communication with the first valve outlet126b.At this time, the delivery container102again urges the drug101into the internal volume136bof the cylinder136until the piston138triggers the end of travel sensor144, thereby causing the digital controller122to again actuate the fluid valve126. Accordingly, the combination of timing and the confirmation that the piston138has travelled a controlled distance allows the flow rate monitor120to effectively act as a flow meter that uses positive displacement instead of complex fluid properties (e.g., localized micro-heating and measurement of heat change with many assumptions in an algorithm such as laminar flow, a lack of bubbles, and/or device orientation that may be incorrect).

The user interface130may include a number of inputs (e.g., buttons) and/or displays that allow a healthcare professional and/or a patient to initially configure the flow rate monitor120. Generally, the interface130includes a limited number of patient-level settings and inputs to reduce user confusion. For example, a healthcare professional may use the interface130to input a desired flow rate, a duration of drug delivery, and/or a risk profile for the specific drug101being administered, and this input or inputs will be transmitted to the digital controller122. In some examples, all or some of this information may be already stored on the digital controller122, and thus the healthcare professional may only need to enter the drug name and/or dosage. As previously stated, the software122aon the digital controller122may be capable of determining desired output values required to operate the flow rate monitor120based on the input or inputs received from the interface130and determine required tolerances (e.g., threshold and/or alarm values). Put another way, the interface130may be configured to only generate an output and may not receive any inputs beyond a selection of a desired drug.

The interface130may additionally include buttons that begin and/or pause operation of the system100so that a user may begin drug administration at a desired time. The interface130may also include a display that can indicates desired and/or actual flow values, error messages, remaining dosage time, and the like. In some examples, the interface may be disposed on or within the flow rate monitor120, or optionally may be implemented via external connectivity (e.g., via a portable electronic device such as a smart phone, computer, tablet, etc.).

The optional alarm132may function as a feedback device to alert the user of a potential problem (e.g., a full and/or partial occlusion) in the system100. The alarm may be in the form of a speaker that produces an audible noise, a buzzer that vibrates, and/or a light that flashes. Other examples are possible. Upon the digital controller122receiving an input value from the user interface130that indicates a desired drug and/or dosage to be administered, the digital controller122may optionally initiate a risk profile corresponding to the selected drug. This risk profile may include an indication of an allowable flow rate range for the particular drug101being administered and/or any additional important operational values associated with the drug. In these examples, upon a user inputting settings (e.g., the particular drug, a desired flow rate, etc.) into the interface130, the digital controller122may determine the appropriate risk profile, which can include an alarm value, via software122a.In the event that the sensed flow value obtained from the end of travel sensors144exceeds this alarm value, the digital controller122may transmit a signal that causes the alarm132to be triggered and/or actuated. For example, the alarm value may be a range of approximately 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, the alarm may be triggered, thus alerting the user to take appropriate action. Advantageously, by using the alarm132, the patient will no long need to restart on a new delivery cycle upon occurrence of an occlusion.

In some examples, the system100may additionally include at least one compliance member in the form of a flexible tube, a diaphragm, and/or a bellows that can absorb high frequency fluid displacement. Some drug delivery systems operating at high frequencies (e.g., more than 50% duty cycle, or where chamber is filling for at least 50% of the time) may benefit from such a compliance member as it may smooth out the delivery pulses which may be desirable for certain drugs. Lower frequency delivery allows sufficient time to ‘equalize’ for more predictable delivery, but for high frequencies (e.g., when using components such as a rigid flow controller system) the compliance member may help.

So configured, the flow rate monitor120may be implemented as an optional component in existing delivery systems100used in a variety of locations including a patient's home, office, or other non-medical facility environment. In some examples, the flow rate monitor120may be water resistant or waterproof to enable use while a user bathes. The flow rate monitor120may be provided with a coiled second supply line that automatically retracts, thus staying out of the way of the user.

Advantageously, the flow rate monitor120provides increased accuracy as compared to conventional reusable systems (e.g., conventional systems have an accuracy of approximately ±15%, while the system described herein may result in an accuracy of approximately ±6%) and may reduce and/or eliminate patient sensitivity to running out of drug101. The flow rate monitor120may allow for a constant pressure to be delivered over longer periods of time. Further, the need to overfill the container102is eliminated due to less wasted medication and feedback in the case of blockage. Advantageously, alarms are minimized through the use of custom risk profile based on the specific drug101.

The flow rate monitor120may be replaced at each refill interval, so battery124needn't occupy a large volume. Accordingly, the flow rate monitor120may have a small, discrete, patient-friendly size that is easy to transport and is suitable for pain management. In some examples, by pairing a relatively high flow displacement pump with the flow rate monitor120, a low duty cycle may be provided that only allows flow for approximately 6% of the overall administration time, thereby reducing amount of time the valve126needs to be powered. Most drug delivery cycles may be averaged over time such that the flow rate monitor120delivers numerous high flow rates for short periods of time, which is the clinical equivalent to constant, low flow rates.

The end of travel sensors144may have additional uses. For example, a pressure differential may be present if the delivery cycle was successful, or equal input/output pressures may be expected if the cycle was unsuccessful. Accordingly, a differential pressure sensor may be positioned on the inlet/outlet lines that determine whether to reject an “increment” to the cycle count that updates the delivered volume. Further example, if the end of travel sensor144indicates an incomplete delivery, and a differential pressure sensor shows a complete delivery, this may be an indicator that one of the end of travel sensors144is experiencing a fault or error. If the end of travel sensor144shows an incomplete delivery and a differential pressure sensor also shows an incomplete delivery, then the output line120bmay be occluded.

Turning toFIGS. 2aand 2b, one example translating syringe128is provided in further detail. In this example, the piston138may include a partially deformable head portion that deforms under fluid pressure, which, in some examples, may provide a desired variation in fluid delivery as the pressure of the delivery container102varies during delivery of the drug101. However, in some examples, such variation may be undesirable. Accordingly, inFIG. 3, a first alternative example sealing mechanism150is provided in the form of any number of O-ring seals disposed around an outer diameter of the piston head139. Further, in this example, the piston head139defines a generally flat, non-deformable facing surface to reduce a likelihood of deformability.

As illustrated inFIGS. 4aand 4b, a second alternative example sealing mechanism250is provided in the form of a spring energized seal. More specifically, a portion of the piston138is surrounded by a spring energized seal250, which engages the piston138and the cylinder136to create a seal. The spring energized seal250includes a body250a,an O-ring disposed on or about an outer perimeter of the body250a,and a spring member250cdisposed within the body250a.By using springs as energizers (e.g., a balseal spring seal), seals may produce minimal stiction or static friction. Such a seal250may use rigid PTFE or similar materials that do not exhibit substantial wait time stiction. Further, the spring energizer allows for reduced contact pressure.

As illustrated inFIGS. 5a-5c,a third alternative example sealing mechanism350is provided in the form of a lip-type seal such as a U-cup. The U-cup seal350may further reduce friction and improve sealing between the piston138and the cylinder136, and may be constructed from PTFE. In some examples, the U-cup seal350may be energized via an elastomeric O-ring354disposed within the cup portion352of the U-cup seal350. As illustrated inFIGS. 6aand 6b, a fourth example sealing mechanism450in the form of glide rings constructed from PTFE may be used in conjunction with an underlying O-ring energizer454to reduce stiction.

As illustrated inFIGS. 7aand 7b, a fifth alternative example sealing mechanism550is provided in the form of a rolling diaphragm as an alternative to a sliding seal. The rolling diaphragm550may result in less running friction and static friction, thus eliminating stiction issues.

As illustrated inFIGS. 8aand 8b, a sixth alternative example sealing mechanism650is provided in the form of an elastic reservoir that includes a stretchable bladder652and a lubricant layer654. By adding the elastic stretchable bladder652, the spring140may be eliminated, thus reducing friction. The lubricant654may reduce friction between the cylinder136hard wall and the bladder652.

The above description describes various devices, assemblies, components, subsystems and methods for use related to a drug delivery device. The devices, assemblies, components, subsystems, methods or drug delivery devices can further comprise or be used with a drug including but not limited to those drugs identified below as well as their generic and biosimilar counterparts. The term drug, as used herein, can be used interchangeably with other similar terms and can be used to refer to any type of medicament or therapeutic material including traditional and non-traditional pharmaceuticals, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules and generics. Non-therapeutic injectable materials are also encompassed. The drug may be in liquid form, a lyophilized form, or in a reconstituted from lyophilized form. The following example list of drugs should not be considered as all-inclusive or limiting.

The drug will be contained in a reservoir. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the drug. The primary container can be a vial, a cartridge or a pre-filled syringe.

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

In other embodiments, the drug delivery device may contain or be used with an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, an ESA is an erythropoiesis stimulating protein. As used herein, “erythropoiesis stimulating protein” means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate erythropoietin receptor; antibodies that bind to erythropoietin receptor and activate the receptor; or peptides that bind to and activate erythropoietin receptor. Erythropoiesis stimulating proteins include, but are not limited to, Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, pegylated erythropoietin, carbamylated erythropoietin, as well as the molecules or variants or analogs thereof.

In some embodiments, the drug delivery device may contain or be used with a sclerostin antibody, such as but not limited to romosozumab, blosozumab, or BPS 804 (Novartis) and in other embodiments, a monoclonal antibody (IgG) that binds 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, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant or panitumumab. In some embodiments, the reservoir of the drug delivery device may be filled with or the device can be used with IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers including but are 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 with endogenous tissue inhibitors of metalloproteinases (TIMPs) such as but not limited to TIMP-3. Antagonistic antibodies for 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 with a drug delivery device of the present disclosure. Additionally, bispecific T cell engager (BiTE®) antibodies such as but not limited to 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 large molecule agonist such as but not limited to apelin or analogues thereof. In some embodiments, a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody is used in or with the drug delivery device of the present disclosure.

Although the drug delivery devices, assemblies, components, subsystems and methods have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the present disclosure. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention(s) disclosed herein.