Patent Application
20250195918
The present disclosure relates to systems and methods for packaging, distribution, storage, administration and/or disposal of a radiopharmaceutical (e.g., a radioactive drug used for therapy or imaging). The present disclosure further relates to systems and methods for packaging, distribution, storage, administration and/or disposal of therapeutic or diagnostic agents requiring precise volumetric delivery from a controlled source. In another embodiment, the present disclosure relates to systems, apparatuses, and methods for delivery and filtration of radiopharmaceuticals in medical injection procedures.
Radiopharmaceuticals can be utilized for targeted radionuclide therapy (TRT) or for diagnostic imaging. A radiopharmaceutical commonly includes a radioisotope (e.g., Ac-255, Lu-177, etc.), a targeting moiety or biovector (e.g., an antibody, a peptide, an antigen, small molecule, etc.), and optionally a chelator (e.g. DOTA, NOTA, DTPA, etc.) linked together into a single structure. In some cases, the TRT can be solely the radioisotope without a biovector or chelator when the radioisotope is one which the human body naturally takes up into tissues or organs. The radiopharmaceutical is configured to interact with a target protein on a cell, such as a cancer cell. The radiopharmaceutical can be mixed in a liquid form or a fluid form. In some examples or aspects, the radiopharmaceutical may be a solid particulate that is entrained in a fluid (e.g., a slurry that is suitable for injection into a patient). Administration is generally via intravenous administration into the systemic circulation.
Examples of TRTs can include targeted alpha therapies (TAT) or targeted beta therapies (TBT). Such therapies can be administered as mono therapies or in combination, such as via simultaneous or sequential administration. The radioactive therapeutic agent for TAT predominantly emits alpha radiation. The remainder of the emitted radiation from the radioactive therapeutic agent for TAT can include gamma radiation and/or beta radiation. A radioactive therapeutic agent for TBT predominantly emits beta radiation. The remainder of the emitted radiation for the radioactive therapeutic agent for TBT can include gamma radiation and/or alpha radiation. Examples of targeted alpha therapies include, without limitation, therapies based on thorium (Th-227) actinium (Ac-225), and lead (Pb-212). Examples of targeted beta therapies include therapies based on lutetium (Lu-177), copper (Cu-67), or iodine (I-131). Other examples of a radioactive therapeutic agents can include an alpha therapeutic agent that utilizes radium (Ra) (e.g. the Ra-223 isotope, such as the XOFIGO® treatment provided by Bayer Health Care). Processes for the preparation, prepared solutions, and use of XOFIGO® are described in U.S. Pat. No. 6,635,234, the disclosure of which is incorporated by reference herein in its entirety.
Radiopharmaceuticals used in TRT can pose significant production, storage, distribution, administration, handling, and disposal challenges. Because the therapeutic agent is radioactive, it can pose a radiation exposure to human health. Moreover, given the decaying nature of radioactive agents, the longer it takes to make, process, and deliver a radiopharmaceutical to a patient, the less activity is present in the administered dose. There are substantial regulations that must be followed to keep the radioactive material safely stored and utilized that can affect how the agent can be stored and transported as well as who may use or administer the radioactive therapeutic agent. For example, such regulations may require a care provider to have hundreds of hours of training in order to be able to administer any TRT.
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The conventional process for distribution and administration of TRT and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source severely limits their applicability and use. After accounting for shipping, handling and patient scheduling, treatment locations will only have a limited time for administering a dose to a specific patient. The challenges imposed by variability in shipping, handling, and patient scheduling may have an impact on the efficacy of the TRT or other therapeutic or diagnostic agents, such as under-dosing at the time of delivery of the pharmaceutical to the patient. Due to these challenges associated with conventional systems and processes for distribution and administration of TRTs and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, there exists a need in the art for improved systems and processes for distribution, handling, administration, and disposal of such therapies.
Additionally, radiotherapy and radiology are rapidly expanding medical fields that utilize radioactive drugs for both treatment and imaging procedures. Delivering radiopharmaceuticals has several challenges. In some situations, radiation given off by the radiopharmaceutical may be dangerous to healthcare workers administering the drug to the patient. In some situations, daughter isotopes or products may be present in the radiopharmaceutical which may be beneficial to remove or reduce before delivery to a patient. An example of this is strontium breakthrough in a rubidium generator, as discussed in U.S. Pat. No. 8,071,959, the disclosure of which is hereby incorporated by reference in its entirety.
Furthermore, various forms of retention of the radiopharmaceutical in the patient can produce less than optimal treatment and/or adverse effects. Retention may include a condition in which the radiopharmaceutical is properly injected into the patient at a vascular, commonly venous access site, but due to various characteristics of the fluid flow and patient physiology, the radiopharmaceutical does not advance through the bloodstream as intended. This can result in a buildup of radioactive particles near the access site, or at other locations within the patient's venous structure. This may be termed stasis, slow clearance, or delayed clearance. Common causes include low blood flow in the vessel or adhesion of the radiopharmaceutical to the vessel wall. Extravasation, another type of retention, is a condition in which the radiopharmaceutical is inadvertently injected into the tissue outside of the target vasculature surrounding the injection site, and can likewise be dangerous to the patient.
Due to the above technical concerns as well as regulatory and training requirements, administration of radiopharmaceuticals is conventionally performed only by highly specialized healthcare workers, making such procedures less accessible than may be desired. Radiotherapy is heavily regulated due to its inherent challenges, and the regulations surrounding procedures are often complex. For example, dosages with an inaccuracy of 10% or more must be reported to appropriate regulatory agencies in some jurisdictions. Due to these challenges associated with conventional systems and processes for distribution and administration of radiopharmaceuticals and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, there exists a need in the art for improved systems and processes for distribution, handling, administration, and disposal of such therapies.
In view of the disadvantages of conventional systems and processes for distribution, handling, administration, and disposal of TRTs and other therapeutic or diagnostic agents, a better supply chain process is needed such that a treatment location can have TRTs available and ready to use for a longer period of time. Furthermore, improved systems and processes are needed to ensure that stored products are no longer patient specific. Instead, the treatment location can be provided equipment to help dose a treatment for any patient that may be in the location on any particular day so that there is more flexibility in how the stored product can be utilized at the treatment location such that an effective dose of the radiopharmaceutical can be delivered to the patient. Such patient-specific dosing is accomplished without the need for treatment location dose calibrators, thereby reducing or eliminating the need for manual measurements and handling within a designated hot lab. The dose, volume, and concentration may be accurately measured at the manufacturing or filling sites where it is much more efficient to use dosing and filling equipment, such as multiple dose calibrators with error detection and correction, automated handling of samples, automated recording of data, and accurate weighing or volume determination. The more accurate equipment and reduction or elimination of the chance for human error increases the reliability of the whole supply chain.
In some embodiments or aspects of the present disclosure, provided is a storage device configured to connect to a delivery system for delivering a therapeutic or diagnostic agent. The storage device may include: a housing having a chamber defined therein and a vessel positioned within the chamber. The vessel may have a distal end opposite a proximal end with an interior defined therebetween and configured for receiving the therapeutic or diagnostic agent. The proximal end of the vessel may have an access port for accessing the interior. The storage device further may have a door associated with the housing, the door being movable relative to the housing between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may reveal the opening in the housing for accessing the access port of the vessel. The storage device further may have a holder within the chamber of the housing and in contact with the vessel to fix the vessel relative to the housing such that the access port of the vessel is positioned at the opening in the housing. The door may be moveable between the closed position and the open position in response to actuation by an access mechanism of the delivery system.
In some embodiments or aspects of the present disclosure, the holder may include a contact element for contacting the distal end of the vessel and a plurality of tabs connected to the contact element and configured to engage an inner surface of the housing to fix the distal end of the vessel relative to the housing. The storage device further may include a plurality of ribs within the chamber of the housing and surrounding the opening. The plurality of ribs may be configured for fixing the proximal end of the vessel relative to the housing.
In some embodiments or aspects of the present disclosure, the storage device further may include a lock for locking the door in one of the open position and the closed position. A door cover may be connected to the housing, wherein the door cover encloses the door within a door chamber. The door cover may include a door access opening having a seal, and a vessel access opening, such as via a spike, positioned opposite the opening in the housing. The seal may be pierceable by the access mechanism of the delivery system.
In some embodiments or aspects of the present disclosure, the storage device further may include a label or a tag or data carrier on the housing that contains machine readable authenticatable data that includes at least one of product information, production information, prescription information, and shipping conditions information. The opening in the housing may be configured to receive a spike extending into the access port for accessing the therapeutic or diagnostic agent when the door is in the open position. In some embodiments or aspects, the therapeutic or diagnostic agent may be a radiopharmaceutical, and wherein the housing includes shielding configured to prevent radiation from the radiopharmaceutical from being emitted out of the housing.
In some embodiments or aspects of the present disclosure, provided is an assembly configured to connect to a delivery system for delivering a therapeutic or diagnostic agent. The assembly may include a storage device containing the therapeutic or diagnostic agent, and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent. The storage device may include a housing having a chamber defined therein and a vessel positioned within the chamber. The vessel may have an interior configured for receiving therapeutic or diagnostic agent and an access port for accessing the interior. The storage device further may include a door associated with the housing, the door movable relative to the housing between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may reveal the opening in the housing for accessing the access port of the vessel. The fluid cassette may include a spike, a metering device, and a fluid path set fluidly connecting the spike to the metering device. The fluid cassette further may include an enclosure enclosing the spike, the metering device, and the fluid path set. The storage device and the fluid cassette may be configured to connect to a delivery system such that the door of the storage device is accessible by an access mechanism of the delivery system and such that the spike and the metering device of the fluid cassette are accessible by a delivery mechanism of the delivery system.
In some embodiments or aspects of the present disclosure, the spike of the fluid cassette may be insertable into access port of the vessel when the door is moved to the open position to fluidly connect the metering device to the vessel via the fluid path set. The fluid path set may include one or more valves operable by the delivery mechanism of the delivery system for regulating fluid flow through the fluid path element. The fluid cassette may be connectable to a saline source.
In some embodiments or aspects of the present disclosure, the storage device may include a guide mechanism configured for positioning the storage device in a desired orientation relative to the fluid cassette. The guide mechanism may include one or more geometric features on the storage device. The one or more geometric features may be configured to mate with corresponding one or more geometric features on the fluid cassette. The one or more geometric features may prevent mating between incompatible system components.
In some embodiments or aspects of the present disclosure, an outlet of the metering device of the fluid cassette may be configured to connect to an infusion set for delivering a dose of the therapeutic or diagnostic agent from the vessel to the infusion set. The storage device further may include a label or a tag on the housing that contains machine readable authenticatable data that includes at least one of product information, production information, prescription information, and shipping conditions information. The therapeutic or diagnostic agent may be a radiopharmaceutical, and wherein the housing includes shielding configured to prevent significant radiation from the radiopharmaceutical from being emitted out of the housing.
In some embodiments or aspects of the present disclosure, provided is a delivery system for delivering a therapeutic or diagnostic agent. The delivery system may include an injector having a delivery mechanism and an access mechanism, and a fluid delivery assembly removably connectable to the injector. The fluid delivery assembly may include a storage device containing the therapeutic or diagnostic agent, and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent. The storage device may include a housing having a chamber defined therein, and a vessel positioned within the chamber. The vessel may have an interior configured for receiving therapeutic or diagnostic agent and an access port for accessing the interior. The storage device further may include a door associated with the housing, the door being movable relative to the housing via the access mechanism of the injector between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may reveal the opening in the housing for accessing the access port of the vessel. The fluid cassette may include a spike, a metering device, and a fluid path set fluidly connecting the spike to the metering device. The fluid cassette further may include an enclosure enclosing the spike, the metering device, and the fluid path set. The spike and the metering device of the fluid cassette may be accessible by the delivery mechanism of the injector for fluidly connecting the interior of the vessel with the metering device via the fluid path set.
In some embodiments or aspects of the present disclosure, the delivery system further includes an injector controller configured to determine a dose of the therapeutic or diagnostic agent to be drawn from the vessel into the metering device based on machine readable authenticated data on the storage device. The injector controller may be further configured to determine a dose of the therapeutic or diagnostic agent to be drawn from the vessel into the metering device based at least one patient parameter. The injector controller may be connected to a hospital network system, hospital enterprise system, or other healthcare network. The injector controller may include a plurality of dosing algorithms for different pre-defined therapies or diagnostic procedures.
In some embodiments or aspects of the present disclosure, the fluid path set may include one or more valves operable by the delivery mechanism of the delivery system for regulating fluid flow through the fluid path element. The fluid cassette may be connectable to a saline or other flushing fluid source. An outlet of the metering device of the fluid cassette may be configured to connect to an infusion set for delivering a dose of therapeutic or diagnostic agent from the vessel to the infusion set. The storage device may be configured to be removably or non-removably connectable to the fluid cassette.
In some embodiments or aspects of the present disclosure, provided is an inventory device for managing storage and disposal of used therapeutic or diagnostic agent. The inventory device may include a cart having a storage compartment that is accessible via a lockable door. The storage compartment may be configured to store one or more disposal containers. Each disposal container may include a storage device with a housing having a chamber defined therein, and a vessel positioned within the chamber of the housing. The vessel may be configured to store a radiopharmaceutical within an interior thereof. A door may be connected to the housing and be movable between an open position and a closed position. In the closed position, the door may entirely enclose the chamber of the housing. The device further may include a fluid cassette having a spike and a metering device. The storage device may be affixed to the fluid cassette such that the spike is inserted into the vessel to fluidly connect the metering device to the vessel. The metering device may be connected to an infusion set used for injecting a dose of the radiopharmaceutical. The infusion set, the storage device, and the fluid cassette may be retained within the disposal container.
In some embodiments or aspects of the present disclosure, the cart may include at least one indicator associated with the storage compartment to indicate whether any of the one or more disposal containers have been stored for a pre-selected storage time period so that a radioactive component of the used therapeutic or diagnostic agent has decayed to a pre-selected safety threshold level. The cart may include wheels having a wheel lock configured to prevent unauthorized or unintended movement of the cart. The wheel lock may be an electronic lock in communication with a controller. The wheel lock may be a mechanical lock having a key or other mechanical lock mechanism. The wheel lock may be operatively connected with the lockable door so that the wheels are unlocked and rollable only after the lockable door is unlocked.
In some embodiments or aspects of the present disclosure, provided is a process for manufacture and distribution of a therapeutic or diagnostic agent. The process may include filling a vessel with the therapeutic or diagnostic agent, positioning the vessel within a chamber of a storage device having a housing, closing the storage device so that the housing fully encloses the vessel within the chamber, shipping the storage device to an administration facility, opening a door of the storage device using an access mechanism of a delivery system, disinfecting an access port of the vessel using a disinfection mechanism of the delivery system, and accessing the therapeutic or diagnostic agent within the vessel via the access port using the delivery system.
In some embodiments or aspects of the present disclosure, accessing therapeutic or diagnostic agent may include piercing the access port using a spike of a cassette connected to the storage device. The process further may include reading a label or a tag on the storage device to determine at least one of product information, production information, prescription information, and shipping conditions information. The process further may include disinfecting the access port by emitting ultraviolet light or outputting a disinfecting material.
In some embodiments or aspects of the present disclosure, provided is a process for storing and disposing of used therapeutic or diagnostic agent. The process may include collecting a storage device that retains a vessel with a remaining portion of the therapeutic or diagnostic agent, a cassette to which the storage device is fluidly connected, and an infusion set for positioning in a disposal container. The process further may include placing a label, tag, or other indicia on the disposal container to indicate date of use; positioning the disposal container having the storage device, the cassette, and the infusion set therein into a storage compartment; and indicating the disposal container is safe to dispose of after a pre-selected decay time period has elapsed. The process further may include reading the label or other indicia to determine at least one of product information, production information, prescription information, and shipping conditions information.
In some embodiments or aspects of the present disclosure, provided is a process for delivering a dose of a therapeutic or diagnostic agent. The process may include inserting a therapeutic or diagnostic agent into a vessel; positioning the vessel within a chamber of a storage device having a housing; closing a door of the storage device so that the housing fully encloses the vessel within the chamber to shield radiation emitted by the radiopharmaceutical from being emitted out of the housing for transportation and storage of the radiopharmaceutical; determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical included with the storage device; and unlocking the door of the storage device to open the housing to access the radiopharmaceutical within the vessel and inject the determined dose into a patient.
In some embodiments or aspects of the present disclosure, accessing the therapeutic or diagnostic agent may include piercing the access port of the vessel using a spike of a cassette connected to the storage device. The process further may include reading a label or a tag on the storage device to determine at least one of product information, production information, prescription information, and shipping conditions information. The process further may include disinfecting an access port of the vessel. Disinfecting the access port may include emitting ultraviolet light or outputting a disinfecting material.
Additional embodiments or aspects of the systems and processes described herein are detailed in one or more of the following clauses:
Clause 1: A storage device configured to connect to a delivery system for delivering a therapeutic or diagnostic agent, the storage device comprising: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel having a distal end opposite a proximal end with an interior defined therebetween and configured for receiving the therapeutic or diagnostic agent, the proximal end having an access port for accessing the interior; a door associated with the housing, the door movable relative to the housing between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel; and a holder within the chamber of the housing and in contact with the vessel to fix the vessel relative to the housing such that the access port of the vessel is positioned at the opening in the housing; wherein the door is moveable between the closed position and the open position in response to actuation by an access mechanism of the delivery system.
Clause 2: The storage device according to clause 1, wherein the holder comprises a contact element for contacting the distal end of the vessel and a plurality of tabs connected to the contact element and configured to engage an inner surface of the housing to fix the distal end of the vessel relative to the housing.
Clause 3: The storage device according to clause 1 or 2, further comprising a plurality of ribs within the chamber of the housing and surrounding the opening, wherein the plurality of ribs is configured for fixing the proximal end of the vessel relative to the housing.
Clause 4: The storage device according to any of clauses 1 to 3, further comprising a lock for locking the door in one of the open positon and the closed position.
Clause 5: The storage device according to any of clauses 1 to 4, further comprising a door cover connected to the housing, wherein the door cover encloses the door within a door chamber.
Clause 6: The storage device according to any of clauses 1 to 5, wherein the door cover comprises a door access opening having a seal, and a vessel access opening positioned opposite the opening in the housing.
Clause 7: The storage device according to clause 6, wherein the seal is pierceable by the access mechanism of the delivery system.
Clause 8: The storage device according to any of clauses 1 to 7, further comprising a label or a tag on the housing that contains machine readable authenticatable data that includes at least one of product information, production information, prescription information, and shipping conditions information.
Clause 9: The storage device according to any of clauses 1 to 8, wherein the opening in the housing is configured to receive a spike extending into the access port for accessing the therapeutic or diagnostic agent when the door is in the open position.
Clause 10: The storage device according to any of clauses 1 to 9, wherein the therapeutic or diagnostic agent is a radiopharmaceutical, and wherein the housing comprises shielding configured to prevent radiation from the radiopharmaceutical from being emitted out of the housing.
Clause 11: An assembly configured to connect to a delivery system for delivering a therapeutic or diagnostic agent, the assembly comprising: a storage device containing the therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, wherein the storage device comprises: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel having an interior configured for receiving the therapeutic or diagnostic agent and an access port for accessing the interior; and a door associated with the housing, the door movable relative to the housing between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel, wherein the fluid cassette comprises: a spike, a metering device, and a fluid path set fluidly connecting the spike to the metering device; and an enclosure enclosing the spike, the metering device, and the fluid path set, and wherein the storage device and the fluid cassette are configured to connect to a delivery system such that the door of the storage device is accessible by an access mechanism of the delivery system and such that the spike and the metering device of the fluid cassette are accessible by a delivery mechanism of the delivery system.
Clause 12: The assembly according to clause 11, wherein the vessel access member of the fluid cassette is insertable into access port of the vessel when the door is moved to the open position to fluidly connect the metering device to the vessel via the fluid path set.
Clause 13: The assembly according to clause 11 or 12, wherein the fluid path set comprises one or more valves operable by the delivery mechanism of the delivery system for regulating fluid flow through the fluid path element.
Clause 14: The assembly according to any of clauses 11 to 13, wherein the fluid cassette is connectable to a saline source.
Clause 15: The assembly according to any of clauses 11 to 14, wherein the storage device comprises a guide mechanism configured for positioning the storage device in a desired orientation relative to the fluid cassette.
Clause 16: The assembly according to clause 15, wherein the guide mechanism comprises one or more geometric features on the storage device, and wherein the one or more geometric features are configured to mate with corresponding one or more geometric features on the fluid cassette.
Clause 17: The assembly according to any of clauses 11 to 16, wherein an outlet of the metering device of the fluid cassette is configured to connect to an infusion set for delivering a dose of the therapeutic or diagnostic agent from the vessel to the infusion set.
Clause 18: The assembly according to any of clauses 11 to 17, further comprising a label or a tag on the housing that contains machine readable authenticatable data that includes at least one of product information, production information, prescription information, and shipping conditions information.
Clause 19: The assembly according to any of clauses 11 to 18, wherein the therapeutic or diagnostic agent is a radiopharmaceutical, and wherein the housing comprises shielding configured to prevent radiation from the radiopharmaceutical from being emitted out of the housing.
Clause 20: A delivery system for delivering a therapeutic or diagnostic agent, the delivery system comprising: an injector having a delivery mechanism and an access mechanism; and a fluid delivery assembly removably connectable to the injector, the fluid delivery assembly comprising: a storage device containing the therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, wherein the storage device comprises: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel having an interior configured for receiving the therapeutic or diagnostic agent and an access port for accessing the interior; and a door associated with the housing, the door movable relative to the housing via the access mechanism of the injector between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel, wherein the fluid cassette comprises: a vessel access member, a metering device, and a fluid path set fluidly connecting the vessel access member to the metering device; and an enclosure enclosing the vessel access member, the metering device, and the fluid path set, and wherein the vessel access member and the metering device of the fluid cassette are accessible by the delivery mechanism of the injector for fluidly connecting the interior of the vessel with the metering device via the fluid path set.
Clause 21: The delivery system according to clause 20, further comprising an injector controller configured to determine a dose of the therapeutic or diagnostic agent to be drawn from the vessel into the metering device based on machine readable authenticated data on the storage device.
Clause 22: The delivery system according to clause 21, wherein the injector controller is further configured to determine a dose of the therapeutic or diagnostic agent to be drawn from the vessel into the metering device based at least one patient parameter.
Clause 23: The delivery system according to clause 21 or 22, wherein the injector controller is connected to a hospital network system.
Clause 24: The delivery system according to any of clauses 21 to 23, wherein the injector controller comprises a plurality of dosing algorithms for different pre-defined therapies or diagnostic procedures.
Clause 25: The delivery system according to any of clauses 20 to 24, wherein the fluid path set comprises one or more valves operable by the delivery mechanism of the delivery system for regulating fluid flow through the fluid path element.
Clause 26: The delivery system according to any of clauses 20 to 25, wherein the fluid cassette is connectable to a saline source.
Clause 27: The assembly according to any of clauses 20 to 26, wherein an outlet of the metering device of the fluid cassette is configured to connect to an infusion set for delivering a dose of the therapeutic or diagnostic agent from the vessel to the infusion set.
Clause 28: The assembly according to any of clauses 20 to 27, wherein the storage device is configured to be removably or non-removably connectable to the fluid cassette.
Clause 29: The delivery system according to any of clauses 20 to 28, further comprising a label or a tag on the housing that contains machine readable authenticatable data that includes at least one of product information, production information, prescription information, and shipping conditions information.
Clause 30: The delivery system according to any of clauses 20 to 29, wherein the therapeutic or diagnostic agent is a radiopharmaceutical, and wherein the housing comprises shielding configured to prevent radiation from the radiopharmaceutical from being emitted out of the housing.
Clause 31: An inventory device for managing storage and disposal of used therapeutic or diagnostic agent, the inventory device comprising: a cart having a storage compartment that is accessible via a lockable door, the storage compartment configured to store one or more disposal containers, each disposal container comprising: a storage device comprising: a housing having a chamber defined therein; a vessel positioned within the chamber of the housing, the vessel configured to store a radiopharmaceutical within an interior thereof; a door connected to the housing, the door movable between an open position and a closed position, wherein, in the closed position, the door entirely encloses the chamber of the housing; and a fluid cassette comprising a vessel access member and a metering device, the storage device affixed to the fluid cassette such that the vessel access member is inserted into the vessel to fluidly connect the metering device to the vessel, the metering device being connected to an infusion set used for injecting a dose of the radiopharmaceutical, wherein the infusion set, the storage device, and the fluid cassette are retained within the disposal container.
Clause 32: The inventory device according to clause 31, wherein the cart comprises at least one indicator associated with the storage compartment to indicate whether any of the one or more disposal containers have been stored for a pre-selected storage time period so that a radioactive component of the used therapeutic or diagnostic agent has decayed to a pre-selected safety threshold level.
Clause 33: The inventory device according to clause 31 or 32, wherein the cart comprises wheels having a wheel lock configured to prevent unauthorized movement of the cart.
Clause 34: The inventory device according to clause 33, wherein the wheel lock is an electronic lock in communication with a controller.
Clause 35: The inventory device according to clause 33 or 34, wherein the wheel lock is a mechanical lock having a key or other mechanical lock mechanism.
Clause 36: The inventory device according to any of clauses 33 to 35, wherein the wheel lock is operatively connected with the lockable door so that the wheels are unlocked and rollable only after the lockable door is unlocked.
Clause 37: A process for manufacture and distribution of a therapeutic or diagnostic agent, the process comprising: filling a vessel with the therapeutic or diagnostic agent; positioning the vessel within a chamber of a storage device having a housing; closing the storage device so that the housing fully encloses the vessel within the chamber; shipping the storage device to an administration facility; opening a door of the storage device using an access mechanism of a delivery system; disinfecting an access port of the vessel using a disinfection mechanism of the delivery system; and accessing the therapeutic or diagnostic agent within the vessel via the access port using the delivery system.
Clause 38: The process according to clause 37, wherein accessing the therapeutic or diagnostic agent comprises piercing the access port using a vessel access member of a cassette connected to the storage device.
Clause 39: The process according to clause 37 or 38, further comprising reading a label or a tag on the storage device to determine at least one of product information, production information, prescription information, and shipping conditions information.
Clause 40: The process according to any of clauses 37 to 39, wherein disinfecting the access port comprises emitting ultraviolet light or outputting a disinfecting material.
Clause 41: A process for storing and disposing of used therapeutic or diagnostic agent, the process comprising: collecting a storage device that retains a vessel with a remaining portion of the therapeutic or diagnostic agent, a cassette to which the storage device is fluidly connected, and an infusion set for positioning in a disposal container; placing a label, tag, or other indicia on the disposal container to indicate date of use; positioning the disposal container having the storage device, the cassette, and the infusion set therein into a storage compartment; and indicating the disposal container is safe to dispose of after a pre-selected decay time period has elapsed.
Clause 42: The process according to clause 41, further comprising reading the label, tag, or other indicia to determine at least one of product information, production information, prescription information, and shipping conditions information.
Clause 43: A process for delivering a dose of a therapeutic or diagnostic agent, the process comprising: inserting a therapeutic or diagnostic agent into a vessel; positioning the vessel within a chamber of a storage device having a housing; closing a door of the storage device so that the housing fully encloses the vessel within the chamber to shield radiation emitted by the radiopharmaceutical from being emitted out of the housing for transportation and storage of the radiopharmaceutical; determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical included with the storage device; and unlocking the door of the storage device to open the housing to access the radiopharmaceutical within the vessel and inject the determined dose into a patient.
Clause 44: The process according to clause 43, wherein accessing the therapeutic or diagnostic agent comprises piercing the access port using a vessel access member of a cassette connected to the storage device.
Clause 45: The process according to clause 43 or 44, further comprising reading a label or a tag on the storage device to determine at least one of product information, production information, prescription information, and shipping conditions information.
Clause 46: The process according to any of clauses 43 to 45, further comprising disinfecting an access port of the vessel.
Clause 47: The process according to clause 46, wherein disinfecting the access port comprises emitting ultraviolet light or outputting a disinfecting material.
Clause 48: A storage device configured to connect to a delivery system, the storage device comprising: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel containing a radiopharmaceutical within an interior thereof, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223; a door associated with the housing, the door movable relative to the housing between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel; and a holder within the chamber of the housing and in contact with the vessel to fix the vessel relative to the housing such that the access port of the vessel is positioned at the opening in the housing; wherein the door is moveable between the closed position and the open position in response to actuation by an access mechanism of the delivery system.
Clause 49: An assembly configured to connect to a delivery system for delivering a radiopharmaceutical, the assembly comprising: a storage device containing the therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, wherein the storage device comprises: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel containing a radiopharmaceutical within an interior thereof, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223; a door associated with the housing, the door movable relative to the housing between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel, wherein the fluid cassette comprises: a vessel access member, a metering device, and a fluid path set fluidly connecting the vessel access member to the metering device; and an enclosure enclosing the vessel access member, the metering device, and the fluid path set, and wherein the storage device and the fluid cassette are configured to connect to a delivery system such that the door of the storage device is accessible by an access mechanism of the delivery system and such that the vessel access member and the metering device of the fluid cassette are accessible by a delivery mechanism of the delivery system.
Clause 50: A delivery system for delivering a therapeutic or diagnostic agent, the delivery system comprising: an injector having a delivery mechanism and an access mechanism; and a fluid delivery assembly removably connectable to the injector, the fluid delivery assembly comprising: a storage device containing the therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, wherein the storage device comprises: a housing having a chamber defined therein; a vessel positioned within the chamber of the housing, the vessel containing a radiopharmaceutical within an interior thereof, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223; and a door associated with the housing, the door movable relative to the housing via the access mechanism of the injector between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel, wherein the fluid cassette comprises: a vessel access member, a metering device, and a fluid path set fluidly connecting the vessel access member to the metering device; and an enclosure enclosing the vessel access member, the metering device, and the fluid path set, and wherein the vessel access member and the metering device of the fluid cassette are accessible by the delivery mechanism of the injector for fluidly connecting the interior of the vessel with the metering device via the fluid path set, wherein the injector comprises an injector controller configured to determine a dose of the radiopharmaceutical based on manufacturing data attached to the housing of the storage device, the injector controller communicatively connected to the injector to control the injector for injecting the dose so that the injected dose that is received by a patient is the dose determined by the injector controller based on the manufacturing data attached to the housing of the storage device.
Clause 51: An inventory device for managing storage and disposal of used radiopharmaceutical, the inventory device comprising: a cart having shelving that is accessible via a lockable door, the shelving configured to store disposal containers, each disposal container comprising: a storage device comprising: a housing having a chamber defined therein; a vessel positioned within the chamber of the housing, the vessel configured to store a radiopharmaceutical within an interior thereof; a door connected to the housing, the door movable between an open position and a closed position, wherein, in the closed position, the door entirely encloses the chamber of the housing; and a fluid cassette comprising a vessel access member and a metering device, the storage device affixed to the fluid cassette such that the vessel access member is inserted into the vessel to fluidly connect the metering device to the vessel, the metering device being connected to an infusion set used for injecting a dose of the radiopharmaceutical, wherein the infusion set, the storage device, and the fluid cassette are retained within the disposal container, wherein the cart comprises indicators for the shelving to indicate which disposal containers have been stored for a pre-selected storage time period so that the radiopharmaceutical has decayed so radioactivity of the material is at or below a pre-selected safety threshold level.
Clause 52: A process for manufacture and distribution of a radiopharmaceutical for a targeted radionuclide therapy or a diagnostic imaging service, the process comprising: filling a vessel with a radiopharmaceutical for a TRT or the diagnostic imaging service, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223; positioning the vessel within a chamber of a storage device having a housing; closing the storage device so that the housing fully encloses the vessel within the chamber; shipping the storage device to an administration facility; opening a door of the storage device using an access mechanism of a delivery system; disinfecting an access port of the vessel using a disinfection mechanism of the delivery system; and accessing the radiopharmaceutical within the vessel via the access port using the delivery system.
Clause 53: A process for storing and disposing of radiopharmaceutical used in a targeted radionuclide therapy or a diagnostic imaging service, the process comprising: collecting a storage device that retains a vessel with a remaining portion of radiopharmaceutical, a cassette to which the storage device is connected, and an infusion set for positioning in a disposal container; placing a label, tag, or other indicia on the disposal container to indicate date of use; positioning the disposal container having the storage device, the cassette, and the infusion set therein into a storage compartment; and indicating the disposal container is safe to dispose of after a pre-selected decay time period has elapsed, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223.
Clause 54: A process for injecting a dose of a targeted radionuclide therapy or a diagnostic imaging service, the process comprising: inserting a radiopharmaceutical into a vessel, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of a free metallic cation of the alkaline earth metal radium-223; positioning the vessel within a chamber of a storage device having a housing; closing a door of the storage device so that the housing fully encloses the vessel within the chamber to shield radiation emitted by the radiopharmaceutical from being emitted out of the housing for transportation and storage of the radiopharmaceutical; determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical included with the storage device; and unlocking the door of the storage device to open the housing to access the radiopharmaceutical within the vessel and inject the determined dose into a patient.
Clause 55: A radiopharmaceutical dosing injection system for a therapeutically or prophylactically effective amount of a free metallic cation of radium-223, according to any preceding clause.
Clause 56: An inventory device for the managing, storage and disposal of a therapeutically or prophylactically effective amount of a free metallic cation of radium-223, according to any preceding clause.
Clause 57: A process further including a therapeutically or prophylactically effective amount of a free metallic cation of radium-223, according to any preceding clause.
In view of the foregoing, there also exists a need for devices, systems, and methods for improved delivery and filtration of radiopharmaceuticals. Additionally, there exists a need for systems for delivery of radiopharmaceuticals that can safely be performed by a broader range of healthcare professionals than is presently possible or allowed by regulatory entities. Embodiments of the present disclosure may improve conventional radiopharmaceutical injection systems and methods in a multitude of ways. Embodiments of the present disclosure may reduce radiation exposure to patients and operators, and provide more awareness to the operator of the dosages, dosage rates, and associated radiation associated with an injection procedure. Embodiments of the present disclosure may mitigate adverse treatment outcomes by automatically and reliably detecting and correcting conditions such as faulty dosages, radiopharmaceutical retention, extravasation, system leaks, and fluid line occlusions. Further, embodiments of the present disclosure may automatically perform test injections to identify these conditions before delivering the full dose of radiopharmaceutical. Embodiments of the present disclosure may also minimize the number of component connections made or separate before, during, and/or after a procedure to reduce possible points of contamination and leakage. Embodiments of the present disclosure may effectively isolate and store radioactive waste for later disposal. Embodiments of the present disclosure may also alleviate supply chains concerns due to the manner in which the radiopharmaceuticals are supplied and removed from the system after use. As a corollary to improvements in patient outcomes, the advantages of the present disclosure may also reduce the burdens of hospital staff in complying with various regulatory burdens, as many regulatory concerns may be addressed automatically by embodiments of the present disclosure. Embodiments of the present disclosure may provide remote access to experienced and/or licensed personnel such as authorized users to enable remote personnel to oversee or activate the preparation and delivery of the drug to meet legal requirements. This may enable more sites and more operators to deliver the drug, thus expanding patient access to the drug. Embodiments of the present disclosure may also perform some of the record keeping and data analysis and exchange functions required. With this background in mind, embodiments of the present disclosure are directed to a fluid injector system.
In some embodiments or aspects of the present disclosure, the present disclosure is directed to various fluid injector delivery systems.
Additional embodiments or aspects of such fluid injector delivery systems described herein are detailed in one or more of the following clauses:
Clause 1′: A fluid injector delivery system comprising: at least one fluid reservoir comprising a first fluid reservoir configured for receiving a radiopharmaceutical; a radiation filter in fluid communication with the at least one fluid reservoir and configured for retaining radioactive particles from the radiopharmaceutical passing though the radiation filter; at least one sensor configured to detect radioactivity in at least one of the first fluid reservoir, the radiation filter, and a fluid path element in fluid communication with the radiation filter; and a controller in operative communication with the at least one sensor, the controller programmed or configured to: receive a radioactivity measurement from the at least one sensor; and determine, based on the radioactivity measurement, that an amount of radioactive particles in at least one of the first fluid reservoir, the radiation filter, and the fluid path element satisfies a predetermined threshold.
Clause 2′: The fluid injector delivery system of clause 1′, wherein the predetermined threshold comprises at least one of: a predetermined prescribed dosage of the radiopharmaceutical; a predetermined safe dosage of the radiopharmaceutical; a predetermined retention amount; a predetermined rate of change of radioactivity over volume of fluid moved through the filter; and a predetermined rate of change of radioactivity over time.
Clause 3′: The fluid injector delivery system of any of clause 1′ or 2′, wherein the controller is further programmed or configured to determine, based on the radioactivity measurement and one or more injection parameters, a cumulative amount of the radiopharmaceutical injected from the first fluid reservoir.
Clause 4′: The fluid injector delivery system of clause 3′, wherein the one or more injection parameters comprise at least one of: an injection rate of the radiopharmaceutical; an injection volume of the radiopharmaceutical; an injection duration of the radiopharmaceutical; a half-life of the radiopharmaceutical; a decay chain of the radiopharmaceutical; an age of the radiopharmaceutical; a total volume of the radiopharmaceutical; a concentration of the radiopharmaceutical; and an initial radioactivity of the radiopharmaceutical.
Clause 5′: The fluid injector delivery system of clause 3′, wherein the controller is further programmed or configured to compare the cumulative amount of the radiopharmaceutical injected to a predetermined prescribed dosage.
Clause 6′: The fluid injector delivery system of clause 3′, wherein the controller is further programmed or configured to adjust an injection rate of the radiopharmaceutical based on the cumulative amount of the radiopharmaceutical injected.
Clause 7′: The fluid injector delivery system of clause 3′, wherein the controller is further programmed or configured to halt an injection procedure in response to the cumulative amount of the radiopharmaceutical injected satisfying the predetermined threshold.
Clause 8′: The fluid injector delivery system of any of clause 1′-7′, wherein the controller is further programmed or configured to determine, based on the radioactivity measurement received from the at least one sensor, a residual level of radioactive particles in the radiation filter or in the fluid path set.
Clause 9′: The fluid injector delivery system of any of clause 1′-8′, wherein the controller is further programmed or configured to determine, based on the radioactivity measurement received from the at least one sensor, that the radiopharmaceutical is in chelation.
Clause 10′: The fluid injector delivery system of any of clause 1′-9′, wherein the at least one sensor comprises: a first sensor associated with the fluid path set upstream of the radiation filter; and a second sensor associated with the fluid path set downstream of the radiation filter, wherein the controller is programmed or configured to determine the amount of radioactive particles retained by the radiation filter by comparing a radioactivity measurement from the first sensor and a radioactivity measurement from the second sensor.
Clause 11′: The fluid injector delivery system of any of clause 1′-10′, wherein the fluid path set comprises an intermediate vessel in fluid communication with the at least one fluid reservoir and located downstream of the at least one fluid reservoir, wherein at least one of the at least one sensors is associated with intermediate vessel so as to detect radioactivity in the intermediate vessel, and wherein the controller is configured to prohibit delivery of the radiopharmaceutical from the intermediate vessel to a patient based on the amount of radioactive particles in the intermediate vessel deviating from the predetermined threshold.
Clause 12′: The fluid injector delivery system of any of clause 1′-11′, wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured for injecting a flushing agent.
Clause 13′: The fluid injector delivery system of any of clause 1′-12′, wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured for injecting another pharmaceutical.
Clause 14′: The fluid injector delivery system of clause 13′, wherein the another pharmaceutical is a protectant.
Clause 15′: The fluid injector delivery system of any of clause 1′-14′, wherein the first fluid reservoir comprises a radiopharmaceutical generator.
Clause 16′: The fluid injector delivery system of any of clause 1′-15′, wherein the first fluid reservoir comprising: a housing having a chamber defined therein; a vessel positioned within the chamber, the vessel having a distal end opposite a proximal end with an interior defined therebetween and configured for receiving the a radiopharmaceutical, the proximal end having an access port for accessing the interior; a door associated with the housing, the door movable relative to the housing between a closed position and an open position, wherein, in the closed position, the door covers an opening in the housing to enclose the chamber of the housing, and wherein, in the open position, the door reveals the opening in the housing for accessing the access port of the vessel; and a holder within the chamber of the housing and in contact with the vessel to fix the vessel relative to the housing such that the access port of the vessel is positioned at the opening in the housing, wherein the door of the first fluid reservoir is moveable between the closed position and the open position in response to actuation by an access mechanism of the fluid injector delivery system.
Clause 17′: A filtration system for a radiopharmaceutical fluid injector system, the filtration system comprising: a radiation filter in fluid communication with at least one fluid reservoir of the radiopharmaceutical fluid injector system, the radiation filter configured for retaining radioactive particles from a radiopharmaceutical received from the radiopharmaceutical fluid injector system; at least one sensor configured to detect radioactivity in at least one of the fluid reservoir, the radiation filter, and a fluid path set in fluid communication with the radiation filter; and a controller in operative communication with the at least one sensor, the controller programmed or configured to: receive a radioactivity measurement from the at least one sensor; and determine, based on the radioactivity measurement, that an amount of radioactive particles in at least one of the fluid reservoir, the radiation filter, and the fluid path set satisfies a predetermined threshold.
Clause 18′: A fluid injector system comprising: at least one fluid reservoir comprising a first fluid reservoir configured for injecting a radiopharmaceutical; a fluid path set in communication with the at least one fluid reservoir, the fluid path set comprising one or more fluid path elements including a catheter configured for insertion into a venous access site of a patient; a patient sensor configured to detect radioactivity in the patient in relation to the venous access site; and a controller in operative communication with the patient sensor and the fluid path set sensor, the controller programmed or configured to: receive radioactivity measurements from the patient sensor; and determine, based on the radioactivity measurements from the patient sensor, a presence or absence of retention of the radiopharmaceutical in the patient.
Clause 19′: The fluid injector system of clause 18′, further comprising a fluid path set sensor configured to detect radioactivity in the fluid path set upstream of the venous access site.
Clause 20′: The fluid injector system of any of clause 18′ or 19′, wherein the controller is further programmed or configured to modify or halt an injection procedure in response to determining the presence of retention.
Clause 21′: The fluid injector system of any of clause 18′-20′, wherein the controller is further programmed or configured to determine, based on the radioactivity measurements from of the patient sensor and the fluid path set sensor, retention of the radiopharmaceutical in relation to the venous access site.
Clause 22′: The fluid injector system of any of clause 19′-21′, wherein the at least one fluid reservoir further comprises a second fluid reservoir configured for injecting a flushing agent, and wherein the controller is programmed or configured to increase the injection of the flushing agent in response to determining retention of the radiopharmaceutical in the venous access site.
Clause 23′: The fluid injector system of any of clause 19′-21′, wherein the controller is further programmed or configured to determine, based on a comparison of the radioactivity measurements from the patient sensor and the fluid path set sensor, a leakage in the fluid path set.
Clause 24′: The fluid injector system of any of clause 19′-21′, wherein the controller is further programmed or configured to determine, based on a comparison of the radioactivity measurements from the patient sensor and the fluid path set sensor, a blockage in the fluid path set.
Clause 25′: The fluid injector system of any of clause 18′-24′, further comprising a reference sensor configured to detect radioactivity in the patient remotely from the venous access site, wherein the controller is programmed or configured to: receive radioactivity measurements from the reference sensor; and determine, based on a comparison of the radioactivity measurements from the patient sensor and the reference sensor, the presence or absence of retention of the radiopharmaceutical into the patient.
Clause 26′: A retention detection system for a radiopharmaceutical fluid injector system, the retention detection system comprising: a patient sensor configured to detect radioactivity in the patient in proximity to a venous access site of a patient; a fluid path set sensor configured to detect radioactivity in a fluid path set of the fluid injector system upstream of the venous access site; and a controller in operative communication with the patient sensor and the fluid path set sensor, the controller programmed or configured to: receive radioactivity measurements from the patient sensor and the fluid path set sensor; and determine, based on the radioactivity measurements from the patient sensor and the fluid path set sensor, a presence or absence of retention of the radiopharmaceutical into the patient.
Further details and advantages of the various examples described in detail herein will become clear upon reviewing the following detailed description of the various examples in conjunction with the accompanying drawing figures.
In
As used herein, the singular form of “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise.
Spatial or directional terms, such as “left”, “right”, “inner”, “outer”, “above”, “below”, and the like, relate to the embodiments or aspects as shown in the drawing figures and are not to be considered as limiting as the embodiments or aspects can assume various alternative orientations.
All numbers used in the specification and claims are to be understood as being modified in all instances by the term “about”. By “about” is meant plus or minus twenty-five percent of the stated value, such as plus or minus ten percent of the stated value. However, this should not be considered as limiting to any analysis of the values under the doctrine of equivalents.
Unless otherwise indicated, all ranges or ratios disclosed herein are to be understood to encompass the beginning and ending values and any and all subranges or subratios subsumed therein. For example, a stated range or ratio of “1 to 10” should be considered to include any and all subranges or subratios between (and inclusive of) the minimum value of 1 and the maximum value of 10; that is, all subranges or subratios beginning with a minimum value of 1 or more and ending with a maximum value of 10 or less. The ranges and/or ratios disclosed herein represent the average values over the specified range and/or ratio.
The terms “first”, “second”, and the like are not intended to refer to any particular order or chronology, but refer to different conditions, properties, or elements.
All documents referred to herein are “incorporated by reference” in their entirety.
The term “at least” is synonymous with “greater than or equal to”.
The term “not greater than” is synonymous with “less than or equal to”.
Some non-limiting embodiments or aspects may be described herein in connection with thresholds. As used herein, satisfying a threshold may refer to a value being greater than the threshold, more than the threshold, higher than the threshold, greater than or equal to the threshold, less than the threshold, fewer than the threshold, lower than the threshold, less than or equal to the threshold, equal to the threshold, etc.
As used herein, “at least one of” is synonymous with “one or more of”. For example, the phrase “at least one of A, B, or C” means any one of A, B, or C, or any combination of any two or more of A, B, or C. For example, “at least one of A, B, or C” includes A alone; or B alone; or C alone; or A and B; or A and C; or B and C; or all of A, B, and C.
The term “includes” is synonymous with “comprises”.
When used in relation to a component of a fluid delivery system such as a fluid reservoir, a syringe, or a fluid line, the term “distal” refers to a portion of said component nearest to a patient. When used in relation to a component of an injector system such as a fluid reservoir, a syringe, or a fluid line, the term “proximal” refers to a portion of said component nearest to the injector of the injector system (i.e. the portion of said component farthest from the patient). When used in relation to a component of a fluid delivery system such as a fluid reservoir, a syringe, or a fluid line, the term “upstream” refers to a direction away from the patient and towards the injector in relation to the normal flow of fluid of the injector system. When used in relation to a component of a fluid delivery system such as a fluid reservoir, a syringe, or a fluid line, the term “downstream” refers to a direction towards the patient and away from the injector in relation to the normal flow of fluid of the fluid delivery system.
As used herein, the terms “communication” and “communicate” may refer to the reception, receipt, transmission, transfer, provision, and/or the like, of information (e.g., data, signals, messages, instructions, commands, and/or the like).
The term “radiopharmaceutical”, as used herein, refers to a pharmaceutical comprising a radionuclide. Radiopharmaceuticals, as discussed herein, are preferably configured to be administered intravenously (i.v.). There are two types of radiopharmaceuticals: diagnostic (or imaging) and therapeutic radiopharmaceuticals, although in some instances, therapeutic radiopharmaceuticals may be used for both. For example, so TRSs may emit gamma radiation which may be used for dosimetry assessments and/or diagnostic purposes. Radiopharmaceutical generally used for imaging, such as the positron emitters, may also be used for therapy. See for example Hioki, T., Gholami, Y. H., McKelvey, K. J. et al. Overlooked potential of positrons in cancer therapy. Sci Rep 11, 2475 (2021).
The term “diagnostic radiopharmaceutical” or “imaging radiopharmaceutical”, as used herein, comprises Gamma emitting imaging radiopharmaceuticals for use in SPECT or SPECT/CT imaging and/or Positron emitting imaging radiopharmaceuticals for use in PET or PET/CT imaging. Examples of Gamma emitting imaging radiopharmaceuticals include, without limitation, technetium (Tc-99m), iodine (I-123), indium (In-111), gallium (Ga-67), or rhenium (Re-186). Examples of Positron emitting imaging radiopharmaceuticals include, without limitation, fluorine (F-18), gallium (Ga-68), zirconium (Zr-89), iodine (I-124), copper (Cu-64), rubidium (Rb-82) or yttrium (Y-86).
The term “therapeutic radiopharmaceutical”, as used herein, comprises Beta Therapeutic Radiopharmaceuticals, Alpha Therapeutic Radiopharmaceuticals, Positron Therapeutic Radiopharmaceuticals, Auger Therapeutic Radiopharmaceuticals, Gamma Therapeutic Radiopharmaceuticals, and/or combinations thereof.
As used herein, the term “therapeutic or diagnostic agent” refers to any diagnostic pharmaceutical, imaging pharmaceutical, a radiotherapy or chemotherapy pharmaceutical, a therapeutic pharmaceutical, or any other liquid or powder (once reconstituted) used in a therapeutic or diagnostic capacity that requires precise dose delivery from a controlled source, where dose is the amount of active ingredient. The dose delivery may be accomplished by precise volumetric delivery.
All radiation shielding is fractional or partial. Adding a half value layer of thickness to the shielding reduces the transmitted radiation by a factor of two. The effectiveness of shielding depends upon the energy of the radiation being shielded. Thus, terms such as “block”, “stop”, or “prevent” radiation transmission or radiation release indicate a reduction in transmitted or released radiation to an acceptable level. This acceptable level may be dependent upon local regulations, requirements, policies, or preferences. The many materials used for shielding and the guidelines involved are well known to those in the health physics field.
The disclosure comprises, consists of, or consists essentially of the following examples of the embodiments or aspects, in any combination. Various examples of the disclosure may be discussed separately. However, it is to be understood that this is simply for ease of illustration and discussion. In the practice of the disclosure, one or more aspects of the disclosure described in one example can be combined with one or more aspects of the disclosure described in one or more of the other examples.
In various embodiments or aspects, the present disclosure is directed to systems and processes for distribution, storage, administration, and disposal of a radiopharmaceutical therapeutic agent. The present disclosure is also directed to systems and processes for distribution, storage, administration, and disposal of other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, such as chemotherapy pharmaceuticals. As discussed herein, conventional process for distribution and administration of therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source severely limits their applicability and use. After accounting for shipping, handling and patient scheduling, treatment locations have a limited time for administering a dose to a specific patient. The systems and processes described herein provide an improvement in the distribution, storage, administration, and disposal of therapeutic or diagnostic agents to allow increased time for administering a dose to a specific patient.
As discussed in various embodiments or aspects of the present disclosure, a storage device can be configured to store a radioactive therapeutic agent from point of production for shipment and storage at a treatment facility so the radioactive therapeutic agent is fully enclosed and encased until use. Each of the storage devices can be sized, shaped, and configured to provide radiation shielding appropriate to the radioactive isotope and dose being stored. The storage devices can also be further packaged and surrounded by additional shielding. The storage device housing is configured to be opened and unsealed only at the treatment site utilizing a dedicated device, as described herein. In some embodiments or aspects, a storage device can be configured to store a therapeutic or diagnostic agent other than a radiopharmaceutical from point of production for shipment and storage at a treatment facility so the therapeutic or diagnostic agent is fully enclosed and encased until use.
As discussed in various embodiments or aspects of the present disclosure, a system can be provided to include a radioactive therapeutic agent injection/infusion system specifically adapted for accessing the therapeutic or diagnostic agent stored in a storage device so the material is only accessible for administering to a patient via the injection/infusion system and is otherwise prevented from being administered if the storage device is not recognized as an untampered storage device. The storage device can be configured so that only the injection/infusion system can open the storage device to access the therapeutic or diagnostic agent for injecting the agent into a patient. When the therapeutic or diagnostic agent is a radiopharmaceutical, the combination of the storage device and injection/infusion system can help ensure the radioactive material remains fully sealed and enclosed from time of production until use. Further, the injection/infusion system and storage device once used can remain connected and unopenable to facilitate safe containment and disposal of radioactive waste after use.
As discussed in various embodiments or aspects of the present disclosure, a system and process can be provided to calculate the dose for a specific patient based on the therapeutic or diagnostic agent being administered, the patient's parameters, such as patient weight, the known manufacturing and/or calibration date, known radioactivity or other property of the therapeutic or diagnostic agent at the time of manufacture, and known current date and time to determine the appropriate dose for the patient for injecting the volume of the therapeutic or diagnostic agent that corresponds to the calculated activity dose of the agent into the patient for the treatment. When the therapeutic or diagnostic agent is a radiopharmaceutical, the unused portion of the radiopharmaceutical and other components that contacted that radiopharmaceutical that may be contaminated can be stored in a disposal container for storage until the radioactivity has degraded to an acceptable level (usually about 10 half-lives of the radioactive isotope) depending upon the initial dose in the storage device. The system and process are configured such that dosing consistency can be assured in that each patient receives the desired amount of therapeutic or diagnostic agent.
As discussed in various embodiments or aspects of the present disclosure, improved systems and processes are provided for assuring that stored product is no longer designed to be or required to be patient specific. Instead, the systems disclosed herein are configured to dose a treatment for any patient that may be in the location on any particular day so that there is more flexibility in how the stored product can be utilized at the treatment location such that an effective dose of the radiopharmaceutical can be delivered to the patient. Such patient-specific dosing is accomplished without the need for dose calibrators, thereby eliminating additional dose assays for preparation of patient ready doses.
As discussed in various embodiments or aspects of the present disclosure, a system and process can be provided to monitor the therapeutic or diagnostic agent that is stored in the disposal container and indicate when the stored material has sufficiently decayed and is safe for throwing away. Once that determination is made, indication to the user can be provided (e.g. software prompts, or an LED light can turn from a red color to a green color or a red LED can be turned off and a green LED can be turned on) so staff can recognize that there is material that is suitable for disposal, locate the material to throw away, and suitably dispose of the material.
As discussed in various embodiments or aspects of the present disclosure, the improved inventory management flexibility associated with the systems and processes described herein permits care providers to more effectively manage inventory, which no longer has to be managed using a simplistic first in/first out approach and/or an approach that requires each stored dose to be provided for only a single, specific patient. Instead, inventory management and use of doses is managed to account for various factors including patient needs to better manage the supply of available doses. For instance, if a particular patient would require a large dose due to the patient's size (e.g. weight, height and weight, body composition, etc.), a newer, more radioactive vial of the therapeutic agent can be selected to administer to the patient so that only one vial (instead of multiple vials) is needed for the injection of a dose into the patient. This can permit the administration to occur more simply (e.g. only use of one injection sequence) and allow for more flexibility in terms of storage management and administration so doses are more efficiently utilized and less waste occurs. In some situations, this type of flexibility may also help reduce the exposure to a clinician during administering of the therapy and minimize the subsequent cleanup process after the patient has received his or her dose.
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In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and dispose of the therapeutic or diagnostic agent, such as a radiopharmaceutical therapeutic or diagnostic agent. The radiopharmaceutical therapeutic or diagnostic agent that can be stored and injected into a patient can be a material that is in a fluid. The radiopharmaceutical can emit primarily alpha radiation or can emit primarily beta radiation. In some embodiments or aspects, the radiopharmaceutical can emit primarily auger radiation or positron radiation and thus secondary gamma radiation. For material that may emit primarily beta radiation, the storage device 200 and the delivery system 100 can be adapted to address secondary X-ray radiation that can be emitted as a result of the shielding of the beta radiation, as described herein. The delivery system 100 can be adapted to address gamma radiation emitted additionally emitted by the radiopharmaceutical. In some examples or aspects, the delivery system 100 can be configured for storage, administration, and disposal of XOFIGO® treatments as well as other TRT treatments that may utilize targeted alpha therapy or a targeted beta therapy. The delivery system 100 may also be configured to work for radioisotopes that may be made at a treatment location for a treatment or a diagnostic service (e.g. a radioisotope with a very short half-life such as technetium-99 or copper-64 that can be used for imaging or other purposes).
In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and dispose of the therapeutic or diagnostic agent that is a radiopharmaceutical, such as an imaging radiopharmaceutical. The imaging radiopharmaceutical may be, in some embodiments or aspects, a Gamma emitting imaging radiopharmaceutical. Gamma emitting imaging radiopharmaceuticals include, without limitation, 99mTc, 123I, 111In, 67Ga, and/or 186Re. In some embodiments or aspects, the imaging radiopharmaceutical may be a Positron emitting imaging radiopharmaceutical. Positron emitting imaging radiopharmaceuticals include, without limitation, 13N, 18F, 68Ga, 89Zr, 124I, 64Cu, 82Rb, and/or 86Y.
In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and dispose of the therapeutic or diagnostic agent that is a radiopharmaceutical, such as a therapeutic radiopharmaceutical. The therapeutic radiopharmaceutical may be, in some embodiments or aspects, a Beta therapeutic radiopharmaceutical. Beta therapeutic radiopharmaceuticals include, without limitation, Lutetium-177, Iodine-131, Yttrium-90, Copper-67, Rhenium-188 and/or Holmium-166. The therapeutic radiopharmaceutical may be, in some embodiments or aspects, an Alpha therapeutic radiopharmaceutical. Alpha therapeutic radiopharmaceuticals include, without limitation, Radium-223, Actinium-225, Thorium-227, Astatine-211, Lead-212 and/or Bismuth-213. The therapeutic radiopharmaceutical may be, in some embodiments or aspects, an Auger therapeutic radiopharmaceutical. Auger therapeutic radiopharmaceuticals include, without limitation, Terbium-161 and/or Iodine-125. In some embodiments or aspects, the radiopharmaceutical is selected from the group consisting of 177Lu-Oxodotreotide, 223Ra dichloride, 18F-Fluciclovine, 123I-Ioflupane, 68Ga-Dotatate, 111In, 99mTc-Tilmanocept, 99mTc-tetrofosmin, 18F-Florbetaben, 99mTc, 90Y-Ibritumomab tiuxetan, 18F-Florbetapir, 153Sm-Lexidronam EDTMP, 131I-Iobenguane MIBG, 89Sr-Chloride. In some embodiments or aspects, the radionuclide of the radiopharmaceutical configured for imaging or therapy use is linked to FAP (fibroblast activation protein), PSMA (prostate specific membrane antigen), DOTA (dodecane tetraacetic acid and its chelating derivatives), HER2 (human epidermal growth factor receptor 2), GPC-3 (glypican-3 protein) or other mechanisms of action with radiopharmaceuticals.
In some embodiments or aspects, the delivery system 100 can be configured to work for radioisotopes that may be made at a treatment location for a treatment or a diagnostic service (e.g., a radioisotope with a very short half-life such as technetium-99m, nitrogen-13, flourine-18, gallium-68 or copper-64) that can be used for imaging or other purposes. These types of radioisotopes tend to have a very short half-life, which requires an imaging provider to prepare the radioisotopes in a hot lab or central radiopharmacy on site for effective use for a diagnostic service. For such an application, the provider may prepare the diagnostic service material on-site. The provider can then insert that material within a vial, place the vial in a storage device, and record and label that storage device to indicate its date of creation fluid volume, concentration, and/or initial radioactivity. The storage device may have a unique device identifier that is used to record the contents information in the software system. That storage device can then be coupled to a cassette, injector, and infusion set as described herein to provide a determined dose to a patient prior to the patient undergoing imaging. The used materials can also be stored etc. in a similar fashion for disposal, as described herein.
Following is a detailed description of various components of the delivery system 100 and how such components permit utilization of the delivery system 100 for an improved distribution, administration, and disposal therapeutic or diagnostic agents.
With continued reference to
The delivery system 100 further includes a third drawer or shelf 112 configured for storing one or more used assemblies 150. Each assembly is configured to minimize the handling of the storage device 200 during workflow. At least one of the first, second, and third drawers or shelves 108, 110, 112 can have radiation shielding material to sufficiently reduce emission or radioactivity outside the cart 102.
With further reference to
The controller 114 may include at least one processor programmed or configured to calculate a dose of a therapeutic or diagnostic agent to be delivered to a specific patient based on patient data and/or data relating to one or more characteristics of the therapeutic or diagnostic agent. The at least one processor of the controller 118 further may be configured to actuate various components of the delivery system 100 to effect a delivery of a dose to a patient according to a programmed protocol for an injection procedure. The controller 118 may include computer readable media, such as memory, on which one or more injection protocols may be stored for execution by the at least one processor.
The controller 114 of the delivery system 100 can be adapted to determine a dose of the therapeutic or diagnostic agent to provide to a patient. The dose can be determined from one or more variables that can be provided to the controller 114 via the one or more input devices 118. For example, patient weight or other patient characteristics can be entered via a keyboard and/or mouse. Ranges of radiopharmaceutical activities of the therapeutic or diagnostic agent can be determined by the controller 114 based on information associated with the label or tag 270, such as a machine readable label (e.g. barcode) or electronic tag (e.g. RFID) attached to the storage device 200 shown in
In some embodiments or aspects, the controller 118 can have different dosing algorithms for different pre-defined treatments. The scanned barcode, read RFID tag, and/or other input provided by a user can be utilized to select the appropriate dosing algorithm to be run for determining the dose for the patient.
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Instead of incorporating the injector 170 into the cart 102, the delivery system 100′ shown in
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For agents that emit beta radiation, the internal structure of the storage device 200 can be designed and configured to prevent X-rays formed from beta radiation from being emitted out of the housing 201. This blocking of beta radiation and X-rays can be affected by an inner structure of the storage device 200, such as a shielding material disposed in the cavity 224. Alternatively, or in addition, the sidewall of the housing 201 can be chosen, such as by selecting the thickness and material properties, to prevent an emissions of X-rays and beta radiation. In some embodiments or aspects, the storage device 200 can have a plurality of spaced shields (e.g. spaced apart shield walls) defined between the chamber 202 and the outer walls of the housing 201. In some configurations, packing or a fluid (e.g. air) can be positioned in the cavity 224 to provide sufficient shielding of X-rays and/or beta radiation.
Alpha radiation is typically not as difficult to block as alpha particles are large, have more limited penetrating power, and generally administered in lower doses than betas. The sidewalls of the housing 201 can be selected to be of a sufficient thickness for shielding the alpha radiation. Additional wall thickness or packing can be provided within the cavity 224 to help secure the vessel 226 in a desired location and/or provide additional shielding as many alpha and beta emitting isotopes or their daughter isotopes also give off gamma radiation to prevent any additional radiation exposure from the radiopharmaceutical being emitted out of the housing. The size of the housing 201 relative to the vessel 226 may be selected so as to set a minimum distance from the exterior of the housing 201 to the vessel 226 in order to reduce user exposure. In general, though, isotopes emit more than one type of radiation or radiation of different energy levels with different penetrating powers. In addition, all isotopes with have some buildup of daughter products between manufacture of the drug and delivery. Thus there may need to be significant gamma shielding for what are nominally alpha or beta emitters. The materials used for shielding and the guidelines involved are well known to those in the health physics field.
With reference to
The vessel 226 has a proximal end 230 having an access port 232 and a closed distal end 234 with an interior 236 defined between the proximal end 230 and the distal end 234. The access port 232 may be a pierceable septum configured to be pierced by a vessel access member or other access mechanism for accessing the therapeutic or diagnostic agent 228 within the interior 236 of the vessel 226, as discussed herein. During manufacture of the therapeutic or diagnostic agent 228, the agent 228 can be filled into the vessel 226 and the vessel 226 can subsequently be sealed via the access port 232 to retain the agent 228 therein. Filling of the vessel 226 can occur after the vessel 226 is connected or positioned within a chamber 201 of the storage device 200, or prior to connecting or positioning the vessel 226 within the chamber 201. In some embodiments or aspects, the access port 232 may be fully sterilized at the point of manufacture. Vessel 226 may also be a plastic vial, a flexible bladder, a collapsible bag, or a prefilled syringe, preferably with a plunger but no handle to reduce the space needed. A benefit of collapsible vessels and prefilled syringes is that as fluid is pulled, the vessel collapses or plunger moves down so that no air needs to be admitted into the vessel as fluid is removed.
With reference to
In some embodiments or aspects, the vessel 226 may be secured at the proximal end 206 of the housing 201 by a plurality of ribs 238 within the chamber 202 of the housing 201 and surrounding the first opening 208. Each of the plurality of ribs 238 may be configured to engage the proximal end 230 of the vessel 226 to fix the position of the access port 232 relative to the first opening 208 of the housing 201.
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In some embodiments or aspects, the door 248 may be movable between three different positions. In an initial position, the door 248 may be closed. In an intermediate position, the door 248 may be moved from the initial (closed) position to an open position to permit access to the vessel 226. In a final position, the door 248 may be moved to a closed position, in which the door 248 is engaged with the door lock 260 to prevent the door 248 from being reopened and any remaining contents in the vessel 226 from being accessed.
With reference to
In some embodiments or aspects, the storage device 200 may have at least one label, tag, or other indicia 270 on the housing 201. While the at least one label, tag, or other indicia 270 is shown in connection with the embodiment of the storage device shown in
In some embodiments or aspects, the storage device 200′ can be configured such that the storage device 200′ is connectable to a fluid cassette only in a particular orientation. In this manner, the access opening 254′ on the door cover 252′ of the storage device 200′ can be properly aligned with the fluid cassette for proper connection of the vessel access member with the access port 232′ on the vessel 226′. With reference to
With reference to
In some embodiments or aspects, at least a portion of the housing 201′ of the storage device 200′ may have a colored portion that may be used for identifying purposes. For example, a particular color on at least a portion of the housing 201′ of the storage device 200′ may be used for identifying the contents of the storage device 200′, such as the type of the therapeutic or diagnostic agent contained therein. In some embodiments or aspects, a particular color on at least a portion of the housing 201′ of the storage device 200′ may be used for identifying the storage device 200′ as a storage device 200′ intended for training purposes only. Such a storage device 200′ would not contain any therapeutic or diagnostic agent but a safe, harmless liquid, optionally with coloring so that its behavior can be visualized.
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In some embodiments or aspects, the storage device 200 and the fluid cassette 300 may be configured to be removably connectable to each other. In other embodiments or aspects, the storage device 200 and the fluid cassette 300 may be configured to be non-removably connectable to each other, such that when the storage device 200 is connected to the fluid cassette 300, the storage device 200 cannot be removed from the fluid cassette 300. This type of interlocked connection helps prevent any undesired contact with the therapeutic or diagnostic agent. Each fluid cassette 300 can be adapted for connection to one storage device 200 or a pair of storage devices 200. In further embodiments or aspects, the fluid cassette 300 may only be fluidly connectable to the storage device 200, without any direct physical connection between housings thereof.
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The flow path of the fluid path set 314 can be structured to facilitate air removal during priming and limit the formation of bubbles within the material being passed from the vessel 226 of the storage device 200 to the syringe 312, for example by limiting abrupt changes or transitions in the internal diameter of the tubing of the fluid path set 314. The flow path of the fluid path set 314 can further be structured to prevent any air bubbles from being passed from the syringe 312 to incorporate a tortuous fluid path to preferentially separate and divert bubbles or with a hydrophobic membrane. The flow path of the fluid path set 314 can be designed to incorporate valves or other fluidic control elements such as passive valve, active valves, one-way valves, diverting valves, pinch valves, rotary valves, stopcocks, or on-off valves.
With continued reference to
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In some embodiments, a second valve 400 may be provided on the auxiliary branch 398 for controlling fluid flow to the valve block 316. In some embodiments or aspects, the valve block 316 can be operated to selectively open or close the first, second, and third ports 388, 390, 392 via the injector 170. Similarly, the second valve 400 may be operable between open and closed positions via the injector 170.
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Once the storage device 200 is coupled to the fluid cassette 300, and the combined assembly 150 is installed in the delivery system 100, the access mechanism 172 of the injector 100 is configured to move the door 248 from the closed position to the open position such that the spike 310 of the fluid cassette 300 can be extended to pierce through the access port 232 of the vessel 226. With reference to
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In some embodiments or aspects, the disinfection source 194 can include a nozzle or sprayer that can spray an antiseptic material onto the access port and/or an agitation mechanism that can wipe an antiseptic agent onto the access port of a pre-selected sanitation time period. The disinfection time period that is selected can be based on the type of antiseptic that is utilized and the time period needed to eliminate a pre-selected set of organisms with that antiseptic or reduce the amount of such organisms to at or below a pre-selected threshold level. In some embodiments or aspects, the antiseptic material may be applied at the manufacturing site via an antiseptic containing absorbent member similar to that in a SwabCap made by ICU Medical, Inc. of San Clemente, California. The door 248 may hold the antiseptic containing absorbant member in contact with the access port. The antiseptic, for example 70% isopropyl alcohol disinfects, then evaporates slowly. The continued presence of the absorbent member held by the door 248 maintains the sterility of the access port. The absorbent member is moved with door 248 to allow access to the access port.
With reference to
After the therapeutic or diagnostic agent is output from the storage device 200 and injected into a patient, materials used to inject the therapeutic or diagnostic agent into the patient are collected for storage and disposal. With reference to
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Once the used materials have been placed within a labeled disposal container 462, the disposal container 462 can be temporarily stored in the cart of the delivery system 100. In some embodiments or aspects, the labeled disposal container 462 may be stored in a disposal locker 476, shown in
In some embodiments or aspects, drawers or shelves 478 of the disposal locker 476 can have at least one indicator 480 (e.g. red and green LEDs) configured to indicate whether a particular disposal container 462 on the drawer or shelf 478 is safe for disposal. For example, a user can scan a bar code of an individual disposal container 462 and provide other input to an inventory management computer 482 to indicate that the individual disposal container 462 has been added to the drawer or shelf 478. The inventory management computer 482 can then determine whether the stored materials within each specific disposal container 462 have decayed sufficiently based on the scanned information related to the used materials (e.g. date of use, etc.) to control the state of the at least one indicator 480. For example, the inventory management computer 482 can control the state of the at least one indicator 480 such that an LED or other indicator means of the at least one indicator 480 indicates the material in the disposal container 462 is too radioactive to throw away (such as by displaying a red color or other message) or such that an LED or other indicator means of the at least one indicator 480 indicates the material in the disposal container 462 can be thrown away (such as by displaying a green color or other message). Such indicia can permit a user to quickly determine whether the disposal container 462 can be thrown away. This can avoid a user having to periodically scan containers or check use dates on the label 474 of each disposal container 462 to determine the disposal status of the disposal container 462.
The disposal locker 476 can have doors 484 to enclose an interior thereof and a locking mechanism 486 for locking the doors 484. In some embodiments or aspects, the locking mechanism 486 may be configured such that only a user with a sufficient credentials can open the doors 484 to access the disposal locker 476. For example, the locking mechanism 486 may be such that the user must have a key to unlock the doors 484 or must have a user badge or access associated with a user log-in to provide input to a controller for unlocking the doors 484.
Among the functions, capabilities and benefits provided by the systems and methods described herein is the minimization of connections that must be made, the minimization of connections that must be separated or broken, and the containment as much as possible of each connection. In some embodiments, methods, or uses of the system, the only connection that is separated is the connection to the patient, and this is preferable only done once all the drug has been delivered and the delivery connection flushed of drug. Thus, there is a much-reduced chance of any drips, spills, or leakage of liquid drug, aerosols, vapors, or gasses being released which may pose a danger to operators or others in the vicinity. Some radioactive daughter products are gasses. Chemotherapeutic aerosols can be a hazard to those in the vicinity.
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At 520, the infusion set 406 is fluidly connected to the fluid path set 314 of the fluid cassette 300 (shown in
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At 524, the delivery system 100 is configured to administer the therapeutic or diagnostic agent to the patient. For example, the syringe 312 may be operated to be filled with the therapeutic or diagnostic agent from the vessel 226 of the storage device 200, and to deliver the therapeutic or diagnostic agent to the patient P via the infusion set 406 based on a pre-determined administration protocol. In some embodiments or aspects, the delivery system 100 can be configured to administer a unit dose to the patient, wherein a unit dose requires a delivery of the entire contents of the vessel 226. In other embodiments or aspects, the delivery system 100 can be configured to administer a non-unit dose to the patient, wherein a non-unit dose requires a delivery of a portion of the entire contents of the vessel 226.
With continued reference to
At 530, the treatment room is cleaned and the delivery system 100 can be readied for another administration procedure. At 532, the disposal container 462 is moved to the disposal locker 476 for further decay-in-place of the radioactive material.
The use of label, tag, or other indicia 270 on storage device 200 for administration of new doses and storage of used material for disposal can also provide sufficient information to prompt the ordering of new doses. For example, an inventory system can include a computer that receives information on the storage devices 200 that have been used, such as based on information contained on the label, tag, or other indicia 270 (shown in
Referring now to
In addition to data, information, and communication system, additional systems 9030 may be medical patient measurement or monitoring systems, for example ECG, pulse oximeter, temperature, motion, hydration state, cardiac output, and/or respiration rate. In some embodiments or aspects, an additional system 9030 may, for example, be a camera on a separate device that observes or monitors a patient. Data about the patient may be used to monitor the patient's state, check for distress, and/or detect the development of an adverse event during the infusion, as discussed in WO 2021/222771 A1, which is fully incorporated herein by reference. Additional systems 9030 may also be a medical measurement system, such as a CT imager, MR imager, ultrasound unit, or similar device which makes measurements of a patient. Additional system 9030 may be a medical output or treatment device which performs a function on or does an action on or to the patient. Such a device may, for example, be one or more infusion pumps that infuses flushing fluids, protectants, and/or other drugs into a different or the same IV in the patient. The infusion pump may infuse additional saline with the goal of establishing a significantly flow into and through the patient's veins to reduce the chance of retention in the vein. A significant flow in adults, whether provided by an additional fusion pump or by the pump(s) of this disclosure is at least 0.1 ml/s, preferable 0.5 ml/s and ideally 1.0 ml/s. The flow rate that may be use is limited by the total desired time of the infusion and the need to not volume overload the patient. In some instances, because of the volume overload risk, it may be desirable to divide the dosing into multiple discrete boluses with a pause or a reduction of saline flow between boluses. Each bolus is a bolus of drug followed by a flush bolus that flushes the drug out of the neighborhood of the venous injection site. In some embodiments it is desirable that the additional system 9030 communicate its status with the system controller 9000. It is further desirable that the controller 9000 be able to activate, program, or control the additional system 9030 so that the overall infusion can be well coordinated. In an embodiment where an additional system 9030 is an infusion pump, that infusion pump may be used in the patency check procedure of
The fluid reservoirs 1020A, 1020B are fluidly connected to a patient P via a fluid path set 1010 comprising various fluid path elements. The fluid path set 1010 includes a T-connection 1012 where outlet lines from the fluid reservoirs 1020A, 1020B merge into a single line for delivery to the patient P. A valve 1014 is incorporated into the T-connection 1102 or located upstream of the T-connection 1012 to prevent radiopharmaceutical from flowing through the T-connection 1012 during priming of the system 1000. Suitable embodiments of the valve 1014 include, for example, a check valve, a high crack pressure valve, or a stopcock. An example of a commercially available component including the T-connection 1012 and valve 1014 is an SSIT-96LV sold by Bayer, AG. Various components of the system 1000 may be configured for single-patient use and/or multi-patient use. For example, portions of the fluid path set 1010 and may be configured for single-patient use, and may be disposed of after each use. The fluid reservoirs 1020A, 1020B may be configured for single-patient use or multi-patient use in various embodiments. Further details of single- and multi-patient configurations of various components in the system 1000 are described in U.S. Pat. Nos. 8,926,569, 9,855,390, 9,173,995, 9,700,670, 9,480,797, 10,039,889, 10,512,721, and 10,668,221, the disclosures of all of which are hereby incorporated by reference in their entireties.
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To prepare the system 1000 for performing an injection procedure, the elements of the fluid path set 1010 are assembled in the general configuration shown in
Once the system is assembled for use, operation is as follows. The assembled fluid path set 1010 is primed before connecting to the patient by pumping fluid from the fluid reservoirs 1020A, 1020B into the fluid path set 1010 to displace any air. Priming may be performed by advancing the plunger 1030A associated with the first fluid reservoir 1020A such that the portion of the fluid path set 1010 from the first fluid reservoir 1020A to the T-connection 1012 is filled with the radiopharmaceutical. The valve 1014, preferably allows air to leave the fluid path element between first fluid reservoir 1020A to the T-connection 1012 and then is closed so that the radiopharmaceutical does not enter the portion of the fluid path set 1010 downstream of the T-connection 1012. After the portion of the fluid path set 1010 from the first fluid reservoir 1020A to the T-connection 1012 has been primed with radiopharmaceutical, the first plunger 1030A is halted and the second plunger 1030B associated with the second fluid reservoir 1020B is advanced so that the remainder of the fluid path set 1010 is filled with the flushing agent, e.g. saline, from the second fluid reservoir 1020B. The second plunger 1030B is then halted and the fluid path set 1010 is fully primed.
Once primed, the fluid path set 1010 may be connected to the patient P, for example via a catheter 1016 of the fluid path set 1010 inserted into a venous access site 1018 of the patient P. In other embodiments, the fluid path set 1010 may be indirectly connected to the venous access site 1018 of the patient P via an interim pump, as will be described herein with reference to
The system controller 9000 may determine the volume of radiopharmaceutical to deliver to the patient P based upon an initial dose and volume or concentration of the drug in the first fluid reservoir 1020A, which is then corrected to account for any radioactive decay experienced by the radiopharmaceutical. The dose and concentration of the radiopharmaceutical may be known or derived from data stored in memory of the system controller 9000, or the system controller 9000 may determine the dose or concentration from radiation measurements taken by the sensors S1, S2 associated with the first fluid reservoir 1020A. The system controller 9000 may determine the volume of radiopharmaceutical in the first fluid reservoir 1020A based upon the position of the first plunger 1030A, which may be obtained from the data element D1 as described herein or from a sensor (e.g. and encoder) associated with the piston actuator 1040 and/or the first plunger 1030A. Additional description of calculating the initial dose and volume or concentration of the radiopharmaceutical are described in U.S. Pat. No. 10,016,618, the disclosure of which is hereby incorporated by reference in its entirety.
In some embodiments, the flushing agent may serve additional functions beyond priming of the fluid path set 1010. The flushing agent may also be injected before the radiopharmaceutical as a test injection to ensure system components are connected as intended and/or that there is good flow form the catheter 1016 into the patient's veins and onto the central circulation. The operator may then confirm with the patient that the flushing agent injection caused no discomfort. The flushing agent may also be injected at the beginning of the injection to fully distend the veins. The flushing agent may also be injected at least partially concurrently with the radiopharmaceutical to promote flow of the radiopharmaceutical through the venous access site 1018 or other port to the central circulation system of the patient P and thus reduce dwell time or exposure time to the injected drug. The flushing agent may also be injected subsequent to injection of the radiopharmaceutical to ensure that all of the radiopharmaceutical which passes the valve 1014 is flushed out of the fluid path set 1010 and into the patient P, ensuring a complete injection of the radiopharmaceutical dosage.
While the system 1000 is described in general herein, further details of particular system components may be found in the description of corresponding components in U.S. Patent Application Publication No. 2008/0294096, U.S. Pat. Nos. 9,005,166, 7,713,232, U.S. Patent Application Publication No. 2021/0338922, International Patent Application Publication No. WO2015/126526, U.S. Patent Application Publication No. 2021/0055431, U.S. Pat. Nos. 9,002,438, 7,813,841, U.S. Patent Application Publication No. 2018/0296751, and U.S. Patent Application Publication No. 2019/0307949, the disclosures of all of which are hereby incorporated by reference in their entireties.
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Once a desired amount of the radiopharmaceutical has been displaced from the first fluid reservoir 1020A, the piston actuator 1040 begins advancing the second plunger 1030B to deliver the flushing agent from the second fluid reservoir 1020B. As the flushing agent advances through the fluid path set 1010 and displaces the radiopharmaceutical, the output signals of the sensors S3, S5 decrease in time region T7 back to substantially zero (or near to their respective background outputs prior to time T1). The output signal of the sensor S4 likewise decreases as the flushing agent flushes radiopharmaceutical from the filter 300, but at least a portion of the trapped isotopic impurities trapped by the filter 3000 during delivery of the radiopharmaceutical remain. Thus, the output signal of the sensor S4 decreases to a substantially constant level indicative of the trapped isotopic impurities at time T8.
With continued reference to
An increase in the output signal of sensor S4 at a lower rate than the calculated, expected increase may be an indication that an insufficient amount of daughter or parent is being removed by the filter 3000. An increase in the output signal of sensor S4 at a higher rate than the calculated, expected increase may indicate a problem with the initial measurement of radiation or that an undesirable amount of the radiopharmaceutical is being removed from the fluid path set 1010 by the filter 3000. In either case, the system controller 9000 may alert the operator to the situation, and either the operator or the system controller 9000 may take appropriate corrective action, for example pausing or terminating the injection procedure.
The output signal of the sensor S4 at time T8 may be also used as an indicator of proper system functioning or a quality assurance indication. For example the output signal of the sensor S4 at time T8 may be used to determine whether the appropriate amount of isotopic impurity was removed and that the appropriate amount of radiopharmaceutical was delivered to the patient (or to an interim pump or container as shown and described in connection with
In embodiments in which the radiopharmaceutical is supplied from a generator, for example a rubidium, gallium or technetium generator, the output signal of the sensor S4 may be used to identify a breakthrough of the parent isotope from the generator. In particular, too high a rate of increase in the output signal of the sensor S4 within the time region T6 or too high a residual output signal of the sensor S4 within the time region T8 may indicate breakthrough of the parent isotope from the generator. The system controller 9000 may be configured to generate an alert informing the operator to stop using that generator. Examples of systems including generators for producing radiopharmaceuticals include U.S. Pat. No. 7,813,841, U.S. Patent Application Publication No. 2018/0296751, and U.S. Patent Application Publication No. 2019/0307949, the disclosures of which are hereby incorporated by reference in their entireties.
Various types of sensors may be used as the sensors S1-S5. Examples include, but are not limited to, diode detectors, Geiger counters, solid state pulse counters, ion chambers, scintillators with photodiodes (e.g. avalanche photodiodes), and SPECT or PET cameras. Alternatively, the sensors S1-S5 may be more complex devices, such as survey meters, electronic dosimeters, and various commercial offerings from Lucerno Dynamics®. Further details of some of these types of sensors are described in U.S. Pat. No. 9,002,438 and U.S. Patent Application Publication No. 2021/0055431, the disclosures of which are hereby incorporated by reference in their entireties. The method of operation of the sensors S1-S5 may be of various complexity, including binary sensing, count or count rate sensing, dose or dose rate sensing, or energy or spectrum sensing. In some embodiments, any of the sensors S1-S5 may be an energy discriminating sensor, which by measuring the energy of the radiation may be able to quantify and differentiate the radiation measurements of the one or more of the isotopes involved. The sensors S1-S5 may be configured to detect various types of radiation pertinent to the injected radiopharmaceutical, such as alpha radiation, gamma radiation, neutrons, and beta radiation (either directly or via bremsstrahlung). The sensors S1-S5 may have detection ranges, i.e. sensitive areas, corresponding to a surface under the sensor, a segment of tube of known volume, or an entire fluid path element (e.g. the filter 3000). The sensors S1-S5 need not all be of the same type and configuration, and in fact it may be beneficial to use different types/configurations of sensors to measure radiation at different locations in the system 1000.
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Referring now to
After the test injection of the radiopharmaceutical has been injected, the flushing agent is then injected to flush the radiopharmaceutical from the test injection, and the output signals of the sensor S3, S6 are monitored for indications of extravasation and/or retention of the radiopharmaceutical. In the absence of extravasation or retention, the output signal of the sensor S6 decreases to a whole body distribution value after the test injection of the radiopharmaceutical has been flushed, for example by time T7. This behavior is shown by the time course of the solid line labeled “S6 normal” in
The system controller 9000 may use predetermined thresholds on the rate of decrease of the output signal of the sensor S6 to differentiate between normal injections, retention (i.e. delayed clearance), and extravasations. The system controller 9000 may alert the operator accordingly. In the case of normal flow through the system, the system controller 9000, either automatically or upon input from the operator, may proceed with injection of the remainder of the dose of radiopharmaceutical. If retention (i.e. delayed clearance) is detected, the system controller 9000, either automatically or upon input from the operator, may still proceed with injection of the remainder of the dose of radiopharmaceutical, but modifications to the injection procedure may be implemented to address the retention condition. For example, the system controller 9000 may reduce the pharmaceutical injection flow rate, while maintaining the total volumetric flow, to promote clearance and reduce accumulation of the radiopharmaceutical in the patient's vessels. Alternatively, the system controller 9000 may increase the flush agent injection rate to promote clearance and reduce accumulation of the radiopharmaceutical in the patient's vessels. If extravasation is detected, the system controller 9000, either automatically or upon input from the operator, may abort the injection procedure. The operator may then attempt to find a new venous access site 1018, or wait until a different time or day to retry the injection.
However, if at time T4, the output signal of the sensor S6 is continuing to rise, the system controller 9000 may determine that either a retention (i.e. slow clearance) or extravasation condition is present because the radiopharmaceutical is not being flushed from the detection range of the sensor S6 by the flow of the flushing agent injected after time T4. As discussed herein, it is difficult to a priori determine whether a sustained increase in the output signal of the sensor S6 after time T4 is the due to extravasation or slow clearance. To make a definitive determination, the system controller 9000 may inject flushing agent between time T4 and T6 while monitoring the output signal of the sensor S6. A decrease in the output signal of the sensor S6 during the injection of flushing agent between times T4 and T6 indicates that the radiopharmaceutical is being flushed from the patient P and therefore the present condition is retention rather than extravasation. A plateau in the output signal of the sensor S6 during the injection of flushing agent between times T4 and T6 indicates that the radiopharmaceutical is not being flushed and, therefore, extravasation has occurred.
If an extravasation condition is determined to the present, the system controller 9000 may abort the injection procedure and/or alert the operator. If retention is determined to be present, the system controller 9000 may alert the operator and, either automatically or under operator guidance, proceed with the injection of the second stage of radiopharmaceutical at time T6. To mitigate further retention of radiopharmaceutical during the second stage of fluid injection, the system controller 9000 may modify the prescribed injection procedure by decreasing the injection flow rate of the radiopharmaceutical, and/or by increasing the simultaneous injection of the flushing agent, as described in connection with
As the second stage of the injection proceeds, beginning at time T6, the system controller 9000 continues to monitor the output signal of the sensor S6 to monitor for extravasation. Even if extravasation did not occur during the first stage of the radiopharmaceutical injection, it is still possible for extravasation to develop in subsequent stages of radiopharmaceutical injection. At time T7, the output signal of the sensor S3 begins to rise as the radiopharmaceutical again enters the detection range of the sensor S3. Similarly, at time T8, the output signal of the sensor S6 begins to rise as the radiopharmaceutical again enters the detection range of the sensor S6. During a normal injection, the output signals of both the sensors S3, S6 plateau during maximum flow of the radiopharmaceutical. The system controller 9000 may monitor the output signal of the sensor S6 at a predetermined time, for example at time T9, for indications of extravasation. In particular, the system controller 9000 may compare the output signal of the sensor S6 at time T9 to the output signal of the sensor S6 at time T4. If retention was present at time T4, the system controller 9000 may record the rate of increase in the output signal of the sensor S6 and consider it as corresponding to retention. Thus, if the output signal of the sensor S6 increases at time T9, the system controller 9000 can compare the rate of increase at time T9 to the learned rate of increase at time T4. If the increase in the output signal of the sensor S6 at time T9 is similar or equal to the increase at time T4, the system controller 9000 can determine that the previous retention is occurring at T9 and may alert the operator and continue the injection. Conversely, if the increase in the output signal of the sensor S6 at time T9 is more rapid than the increase at time T4, the system controller 9000 can determine that extravasation is occurring at time T9. In some embodiments, the system controller 9000 may use a threshold based on the output signal at time T4 to distinguish between retention and extravasation at time T9. For example, the system controller 9000 may determine that extravasation has occurred at time T9 if the rate of increase of the output signal of the sensor S6 at time T9 exceeds that rate of increase of the output signal at time T4 by a predetermined percentage.
If the system controller 9000 determines that extravasation is occurring at time T9, or at any time thereafter, the system controller 9000 may pause, hold, or abort the injection and alert the operator until subsequent action can be determined. If the rate of increase of the output signal of the sensor S6 at time T9 is similar to or less than the rate of increase of the output signal at time T4, the system controller 9000 may proceed to the conclusion of the injection procedure.
An alternative method of using the sensor S6 to monitor the system 1000 for extravasation can also be understood from
Various valves V1-V10 may be located throughout the fluid path set 1010 and operated by the system controller 9000 to control the flow of fluid(s) through the various fluid path elements, fluid reservoirs 1020A, 1020B, 1020D, 1020E, and bulk fluid sources 1012A, 1012B, 1102D, 1012E. The valves V1-V10 may be active valves such as pinch valves or stepper motor rotary actuated stopcocks, passive valves such as stopcocks, or manually activated valves.
One of more of the auxiliary fluid reservoirs, for example the auxiliary fluid reservoir 1020E shown in
With continued reference to
With continued reference to
As described herein, the system controller 9000 of the any of the embodiments of the systems 1000 illustrated in
In some examples, the system controller 9000 may be configured to determine a cumulative amount of radiopharmaceutical injected from the first fluid reservoir 1020A or the interim fluid reservoir 1020C. The system controller 9000 may make this determination based on the radiation measurements from one or more of the sensors S1-S7 and one or more injection parameters. Example injection parameters include an injection rate of the radiopharmaceutical, an injection volume of the radiopharmaceutical, an injection duration of the radiopharmaceutical, a half-life of the radiopharmaceutical, a decay chain of the radiopharmaceutical, an age of the radiopharmaceutical, a volume of the radiopharmaceutical, a concentration of the radiopharmaceutical, and an initial radioactivity of the radiopharmaceutical. During or after the injection, the system controller 9000 may compare the cumulative amount of the radiopharmaceutical injection to a prescribed dosage as a confirmation check. In some examples, the system controller 9000 may be configured to record, report to the user, or communicate to external systems any or all of the information related to the injection, including, for example, one or more injection parameters.
In some examples, the system controller 9000 may be configured to determine, based on the radioactivity measurement received from one of the sensors S3-S5, a residual level of radioactive particles in the radiation filter 3000 or in the fluid path set 1010. In some examples, the system controller 9000 may be configured to determine, based on the radioactivity measurement received from one or more of the sensors S1-S7, that the radiopharmaceutical is in chelation. In some examples, the system controller 9000 may be configured to determine an amount of radioactive particles suspended in the filter 3000 by comparing a radioactivity measurement from the sensor S3 and a radioactivity measurement from the sensor S5.
In some examples, the system controller 9000 may be configured to determine the presence of retention or extravasation in relation to the venous access site 1018 based on radiation measurements received from at least one of the sensors S3-S6. In particular, the system controller may come the radiation measurements from the sensor S3 in the fluid path set 1010 and the sensor S6 at the venous access site 1018. In some examples, the system controller 9000 may be configured to detect a blockage or leakage in the fluid path set 1010 based on radiation measurements received from at least one of the sensors S3-S6. In particular, the system controller 9000 may determine from a lack of radiation measurement at any of the sensors S3-S6 that the radiopharmaceutical has not reaches that sensor as intended, indicating a leak or blockage. Additionally, a significant increase the radiation measurement of any of the sensors S3-S5 in the fluid path set 1010 may indicate an accumulation of the radiopharmaceutical due to a blockage.
It is noted that the various embodiments of the system 1000 described herein are illustrated schematically, and the various components are positioned relative to one another in a manner to clearly illustrate the operation of the system 1000. However, the arrangement of components in actual practice may vary, and individual components may be stored in different rooms and even in totally different sites. For example, the fluid reservoirs 1020A, 1020C, 1020D, 1020E containing radioactive substances may be stored in a separate room from the patient P to avoid unnecessary radiation exposure to the patient P and operator. The system controller 9000 may include components such as servers and memory connected with wires and/or wirelessly to the at least one processor from remote locations. Further, the system controller 9000 may be connected to and share information with wearable devices such as smart phones, smart watches, etc.
The various fluid reservoirs 1020A-1020E have generally been described as syringe-piston-plunger devices, though any form of fluid pump and reservoir could be used. For example, any of the fluid reservoirs 1020A-1020E could include a bottle, bag, syringe, or tube with a peristaltic pump for fluid delivery or a pressurized reservoir. Fluid pumps such as peristaltic, diaphragm, and piston may be used. In general, positive displacement pumps may be used and non-positive displacement pumps combined with sufficiently accurate flow or volume meters may be used. As noted herein, the first fluid reservoir 1020A containing the radiopharmaceutical may alternatively be a generator for producing the radiopharmaceutical with fluid driven or drawn through it.
Embodiments of the system 1000 described herein may be used for injection of a wide variety of radiopharmaceuticals, particular details of which are described in the various patent documents incorporated by reference. Such radiopharmaceuticals may include, for example, various isotopes of technetium, thorium, actinium, radium, and rubidium. Depending on the isotope and injection procedure, prescribed dosages can range from fractions of a milliliter (mL) to 10s of milliliters, for example approximately 7 mL.
In light of the above, the various fluid delivery systems of the present disclosure permit for an improved method to treat various medical issues and, in particular, to methods and systems for radiotherapy delivery as radiotherapy is set to expand by a factor of up to about 10× in the near future. Given this potential increase in the need for radiotherapy to treat various medical conditions, there is a need to expand the places and people who can supervise and/or administration radiopharmaceuticals. Furthermore, the fluid delivery systems of the present disclosure may be designed to: (i) reduce the radiation exposure received by the operator/administrator; (ii) provide the operator/administrator a better awareness of the dose and/or dose rate of a radiopharmaceutical given to a particular patient; and/or (iii) provide for one or more separate filters, one or more separate sensors, and/or one or more separate controllers so that the fluid delivery systems of the present disclosure are able to handle any isotope-based radiopharmaceutical. Furthermore, the fluid delivery systems of the present disclosure may be designed to reduce the connections to be made and reduce, eliminate, or prevent the disconnections made after a procedure is competed to reduce the chance of leakage or transmission of any dangerous materials to the operator or the environment.
Additionally, the various fluid delivery systems of the present disclosure may present embodiments where dose calibrators may be eliminated as such dose calibrators can be expensive and/or onerous to maintain. Thus, in one instance, the various fluid delivery systems of the present disclosure permit are able to function with multiple syringes of various volumes between 5 mL-65 mL. In another instance, the various fluid delivery systems of the present disclosure may present embodiments where it enables an operator/administrator to deliver: (i) cytoprotective and other preparatory drugs; (ii) deliver sensitizing drugs; (iii) pause and restart an infusion mid treatment without loss of info and/or accuracy (e.g. a pause flushes various lines before opening); and/or (iv) detect one or more leaks.
In still another instance, the various fluid delivery systems of the present disclosure enable an operator/administrator to realize patient customized doses based on one or more factor including, but not limited to, weight, infusion rate, total volume, and/or to realize the ability to select a desired flow rate depending on one or more patient conditions and/or factors (e.g. proteins require slower infusions) and/or supply a patient with more or less saline depending upon individual patient requirements and/or various treatment requirements.
In still another instance, the various fluid delivery systems of the present disclosure enable an operator/administrator a wide array of other types of drugs beyond radiopharmaceuticals including, but not limited to, one or more imaging drugs (e.g. CT contrast, MR contrast, ultrasound contrast, etc.), chemotherapy drugs, immune-regulatory drugs (e.g., drugs for one or more autoimmune disorders including, but not limited to, control Crohn's, ulcerative colitis, rheumatoid arthritis, Lupus, multiple sclerosis, etc.). In still another instance, the various fluid delivery systems of the present disclosure may be used to deliver: (i) Sirtex spheres for the treatment of solid tumors and the like; and/or (ii) prefilled single use patient doses.
In still another instance, the various fluid delivery systems of the present disclosure enable the use of any electronically readable sensor including, but not limited to, an electronic dosimeter, a Lucerno device, an ion chamber, a scintillator with photo diode or avalanche photo diode, etc. In still another instance, the various fluid delivery systems of the present disclosure enable radiation sensing, real-time or otherwise, of alpha, beta directly, beta braking radiation (e.g. deceleration radiation or bremsstrahlung), gamma, and/or neutrons. In still another instance, the various fluid delivery systems of the present disclosure utilize various radiation sensing modes via various methods and/or devices including, but not limited to, pulse count, current, pulse height (charge) measurement, Geiger counter, solid state pulse counter (CZT), diode current measurement, a suitable type of gamma ray spectrometer, Lucerno extravasation detector, a ThermoFischer Scientific sensor, a Berkley nucleonics sensor, and/or an RFID radiation sensor.
Referring now to
In one embodiment, remote system 9050 comprises an offsite controller 9052, a user interface 9060, and additional systems 9080 that can be controlled by a remote operator OP2 as discussed herein. Controller 9052, interface 9060, and additional system 9080 can be the same or different than those located onsite and are formed from any of the possibilities discussed above with regard to the similarly labeled onsite components of 9000, 9010, 9030, and OP1. Further embodiments of the present disclosure may make use of various remote, or virtual, cockpits disclosed and described in detail in U.S. Provisional Patent Application No. 63/336,512, filed Apr. 29, 2022, the disclosure of which is incorporated by reference herein in its entirety.
Although embodiments or aspects have been described in detail for the purpose of illustration and description, it is to be understood that such detail is solely for that purpose and that embodiments or aspects are not limited to the disclosed embodiments or aspects, but, on the contrary, are intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. Various methods of operating various systems of this disclosure are described through one or more exemplary embodiments. These methods of operation are applicable to all embodiments which provide sufficient components for such operation. In some embodiments, more components or elements may be present than are required to implement a particular method. Embodiments of this disclosure may be simplified based on the functions which are to be supported or required in a particular situation. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment or aspect can be combined with one or more features of any other embodiment or aspect. In fact, many of these features can be combined in ways not specifically recited in the claims and/or disclosed in the specification. Although each dependent claim listed below may directly depend on only one claim, the disclosure of possible implementations includes each dependent claim in combination with every other claim in the claim set.
The present application claims priority to U.S. Provisional Application No. 63/312,145, filed on Feb. 21, 2022; U.S. Provisional Application No. 63/312,151, filed on Feb. 21, 2022; U.S. Provisional Application No. 63/312,152, filed on Feb. 21, 2022; and U.S. Provisional Application No. 63/312,148, filed on Feb. 21, 2022, the disclosures of which are incorporated by reference herein in their entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2023/062889 | 2/20/2023 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63312145 | Feb 2022 | US | |
| 63312148 | Feb 2022 | US | |
| 63312151 | Feb 2022 | US | |
| 63312152 | Feb 2022 | US |
