Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
  • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
  • A61M5/142—Pressure infusion, e.g. using pumps
  • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
  • A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/025—Digital circuitry features of electrotherapy devices, e.g. memory, clocks, processors
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/0404—Electrodes for external use
  • A61N1/0408—Use-related aspects
  • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/08—Arrangements or circuits for monitoring, protecting, controlling or indicating
• • G—PHYSICS
  • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
  • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
  • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
  • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
  • G16H20/17—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
  • A61M5/142—Pressure infusion, e.g. using pumps
  • A61M2005/14208—Pressure infusion, e.g. using pumps with a programmable infusion control system, characterised by the infusion program
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
  • A61M5/142—Pressure infusion, e.g. using pumps
  • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
  • A61M2005/14264—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body with means for compensating influence from the environment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M2205/00—General characteristics of the apparatus
  • A61M2205/16—General characteristics of the apparatus with back-up system in case of failure
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M2205/00—General characteristics of the apparatus
  • A61M2205/17—General characteristics of the apparatus with redundant control systems

Definitions

• a switch-operated therapeutic agent delivery device can provide single or multiple doses of a therapeutic agent to a patient by activating a switch. Upon activation, such a device delivers a therapeutic agent to a patient.
• a patient-controlled device offers the patient the ability to self- administer a therapeutic agent as the need arises.
• the therapeutic agent can be an analgesic agent that a patient can administer whenever sufficient pain is felt.
• patient controlled analgesia is patient controlled intravenous infusion, which is carried out by an infusion pump, which is pre-programmed to respond to the instructions of a patient within certain predetermined dosing parameters.
• intravenous infusion pumps are commonly used for control of postoperative pain.
• the patient initiates infusion of a dose of analgesic, which is typically a narcotic, by signaling a control unit.
• the unit receives the signal and, if certain conditions are met, begins infusion of the drug through a needle that has been inserted into one of the patient's veins.
• electrotransport e.g., iontophoresis, also referred to as iontophoretic drug delivery
• a therapeutic agent is actively transported into the body by electric current.
• electrotransport include iontophoresis, electroosmosis and electroporation.
• Iontophoresis delivery devices typically comprise at least two electrodes connected to reservoirs, a voltage source, and a controller that controls delivery of the therapeutic agent by applying the voltage across the pair of electrodes.
• a charged therapeutic agent drug
• at least one reservoir contains a counter-ion and no therapeutic agent.
• the therapeutic agent which is a charged species, is driven from the reservoir containing the therapeutic agent and into and across the skin into the patient to whom the reservoirs are attached.
• the reservoirs may contain other charged and uncharged species.
• the reservoirs are often hydrogels, which contain water as a necessary constituent.
• the reservoirs may also contain electrolytes, preservatives, antibacterial agents, and other charged and uncharged species.
• any patient-controlled drug delivery device and particularly an electrotransport device delivering a therapeutic agent (e.g., an opoid analgesic such as fentanyl) be tightly regulated to prevent the inadvertent delivery of agent to a patient.
• a therapeutic agent e.g., an opoid analgesic such as fentanyl
• short circuits in the device may result in erroneous, additional delivery of drug.
• patient-activated dosing systems must include a dose switch that is selected, e.g., pushed, by a patient to deliver a dose, one particularly vulnerable aspect is this switch.
• a short circuit in the dose switch circuit could be interpreted by control lo ⁇ ic (e.g., processor) of the device as valid dose switch presses, and potentially cause the system to deliver a dose even without a valid patient request. Such short circuits could be caused by contamination or corrosion.
• Described herein are methods and apparatuses (e.g., system and devices) that validate the integrity of a dose switch circuit and signal characteristics prior to initiating a dose.
• the apparatuses and methods described herein perform validation before each dose initiation, and the validation process (e.g., measurements used to determine if the switch is properly functioning) do not interfere with normal operation, including in particular actual presses of the dose switch.
• the apparatus and methods described herein are demonstrably reliable to a high degree of certainty. These apparatus and methods may therefore address the issues raised above.
• the present invention addresses a need in the art of patient-controlled drug administration devices, especially those devices that are subject to humidity and other contaminants during storage and use, such as iontophoresis devices.
• the inventors have identified contaminants present in storage and use of iontophoresis devices, as being particularly problematic, as they can cause the device to malfunction.
• contaminants present in storage and use of iontophoresis devices as being particularly problematic, as they can cause the device to malfunction.
• electrotransport such as iontophoresis - and on-demand drug delivery in general - faulty circuitry can be especially problematic, as it can, in some instances, cause the device to fail to deliver a full dose, to deliver more than the desired dose, to deliver one or more doses during storage, to deliver one or more doses in the absence of a patient instruction, etc.
• the potential for contamination of electronic circuitry is especially present in iontophoretic drug delivery systems, as the reservoirs employed contain water as well as other charged and uncharged species - such as charged therapeutic agent, electrolytes, preservatives and antibacterial agents - which can contaminate circuitry, such as activation switches, circuit leads, circuit traces, etc.
• circuitry such as activation switches, circuit leads, circuit traces, etc.
• More drug delivery methods such as patient-activated pumps, can present similar potential for contamination, especially with environmental humidity and airborne contaminants.
• contaminants can cause current leaks, short circuits ("shorts", including intermittent shorts) and other spurious signals that can interfere with the proper operation of the device.
• the inventors have identified a particular part of the circuitry—the activation switch, as a point that is in some cases especially vulnerable to contamination and malfunction.
• the inventors have further identified the activation switch as a part of the circuitry that is a focal point for detecting and averting potential and actual circuit faults before they negatively impact device performance, and ultimately, patient health.
• Embodiments of the device and methods described herein address the issues raised above by providing means to actively seek out and detect circuit faults and precursors to faults.
• the means employed involve performing active checks of the device circuitry while the device is powered on, e.g. before, during or after drug delivery.
• Some embodiments of the device and methods described herein provide for active detection of circuit faults and/or precursors to faults after any button push or after any event that mimics a button push, such as a spurious voltage.
• Some embodiments provide for active detection of circuit faults or precursors to faults, for instance, between button pushes in an activation sequence, during drug delivery, and between drug delivery sequences (i.e. after one dose has been delivered and before commencement of delivery of another dose).
• the active testing during use of the device is in addition to testing during or following device manufacturing.
• therapeutic agent delivery devices such as electrotransport device (e.g. an iontophoresis device), which may include a housing and components adapted for containing and delivering the therapeutic agent to a patient, a processor for controlling delivery of the therapeutic agent to the patient, and circuitry and/or control logic for detecting one or more faults and/or precursors to faults during device operation, and for disabling the device upon detection of a fault or a precursor to a fault.
• the device is an iontophoresis device or other electrotransport device.
• the device further comprises an alarm for alerting a patient and/or caregiver that the device has detected a fault and/or precursor to a fault.
• the device further comprises an alarm for alerting a patient and/or caregiver that the device is being disabled.
• the either or both alarms are at least one of: an audible tone (or tones), at least one visual indicator, or a combination of two or more thereof.
• the means for containing and delivering therapeutic agent to the patient includes one or more therapeutic agent reservoirs connected to one or more electrodes for applying a current to the reservoirs and actively transporting therapeutic agent across an outer surface of a patient, such as the skin.
• the means for detecting a fault or a precursor to a fault is configured to detect a fault in a switch, such as an activation switch, or other circuit component, such as a trace, a connector, a power supply, an integrated circuit, a lead, a chip, a resistor, a capacitor, an inductor or other circuit component.
• the means for controlling delivery of the therapeutic agent comprises a preprogrammed or programmable integrated circuit controller, such as an ASIC.
• the circuitry described herein is incorporated into a device for delivery of a therapeutic agent (drug) to a patient.
• the device is a patient-activated drug delivery device.
• the device is an electrotransport drug delivery device.
• the drug delivery device is an iontophoretic drug delivery device.
• the drug to be delivered is an opioid analgesic.
• the opioid analgesic is a pharmaceutically acceptable salt of fentanyl or sufentanil, such as fentanyl hydrochloride.
• the methods described herein are executed by a device processor, which may include or be referred to as a controller, especially a controller of a device for delivery of a therapeutic agent (drug) to a patient.
• the methods are carried out by the controller during one or more stages of drug delivery - e.g., during the period of time between pushes of an activation button, during delivery of the drug, between delivery sequences, etc.
• the testing is carried out after any button push or anything that appears to be a button push.
• the methods are under active control of the controller, meaning that the controller initiates detection of faults and precursors to faults in the circuitry, e.g.
• the controller upon detection of a fault or precursor to a fault, takes appropriate action, such as setting a fault detection flag, logging the fault in memory for retrieval at a later time, setting a user warning (such as an indicator light and/or audible tone), and/or disabling the device.
• a fault detection flag such as a fault detection flag
• logging the fault in memory for retrieval at a later time
• setting a user warning such as an indicator light and/or audible tone
• disabling a device upon detection of a fault are described in United States Patent No. 7,027,859 to McMchols et al., which is incorporated herein in its entirety; in particular column 6, line 65 through column 1 1, line 35 are specifically incorporated by reference as teaching various ways to disable a circuit.
• switch operated devices such as a drug delivery device (e.g., a drug delivery pump or iontophoresis device) comprising: (a) a device switch configured to be operated by a user, which provides a switch signal to a switch input of a device controller when operated by a user; (b) the device controller, having said switch input operatively connected to the switch, and configured to receive the switch signal from the switch, the device controller being configured to actuate the device when the switch signal meets certain predetermined conditions and to control and receive signals from a switch integrity test subcircuit; and (c) the switch integrity test subcircuit, which is configured to detect a fault or a precursor to a fault in the switch and provide a fault signal to the controller.
• a drug delivery device e.g., a drug delivery pump or iontophoresis device
• the controller When the controller receives a fault signal from the switch integrity test subcircuit, it executes a switch fault subroutine when a fault or a precursor to a fault is detected.
• the switch integrity test subcircuit is configured to check for and detect a fault or a precursor to a fault in the switch.
• the switch integrity test subcircuit is configured to test for and detect at least one fault or precursor to a fault such as contamination, short circuits, (including intermittent short circuits), compromised circuit components (including malfunctioning resistors, integrated circuit pins, and/or capacitors), etc.
• the switch integrity test subcircuit is configured to test for and detect a voltage (or change in voltage) between the switch input and ground or some intermediate voltage above ground, a short between the switch input and a voltage pull up or some intermediate voltage below the pull up voltage.
• the switch integrity test subcircuit is configured to test for and detect a voltage (or change in voltage) between the switch input and some intermediate voltage above ground (a low voltage, V L ) and/or a short between the switch input and a some intermediate voltage below the pull up voltage (high voltage V H ).
• the switch integrity test subcircuit is able to detect a non-determinant signal that indicates contamination (e.g.
• the switch fault subroutine includes at least one of: activating a user alert feature, logging detection of faults or precursors to faults, deactivating the device, or one or more combinations thereof.
• the controller is configured to measure a voltage or a rate of change of voltage at the switch input and execute the switch fault subroutine when the voltage or rate of change of voltage at the switch input fails to meet one or more predetermined parameters.
• the device is an iontophoresis delivery device comprising first and second electrodes and reservoirs, at least one of the reservoirs containing therapeutic agent to be delivered by iontophoresis.
• the predetermined conditions for actuating the device include the user activating the switch at least two times within a predetermined period of time.
• the switch input is pulled up to a high voltage when the switch is open and the switch input is a low voltage when the switch is closed.
• Some embodiments described herein provide a method of switch fault detection in a switch operated device, said device comprising: (a) a device switch connected to a switch input of a device controller; (b) the device controller comprising said switch input; and (c) a switch integrity test subcircuit, said method comprising said controller: (i) activating the switch integrity test subcircuit; (ii) detecting a voltage condition at the switch input; and (iii) activating a switch fault subroutine if the voltage condition at the switch input fails to meet one or more predetermined conditions.
• the steps of activating the switch integrity test subcircuit and detecting a voltage condition at the switch input are executed continuously or periodically throughout use of the device.
• the switch fault subroutine includes, for example, activating a user alert feature, logging detection of faults or precursors to faults, deactivating the device, or one or more combinations thereof.
• the voltage condition is a voltage, a change in voltage or both.
• the controller detects the voltage at the switch input under conditions in which the voltage should be zero or nearly zero if the switch integrity is within operating norms, and activates the switch fault subroutine if the voltage is significantly higher than zero.
• the controller detects the voltage at the switch input under conditions in which the voltage should be equal to a pull up voltage or nearly equal to the pull up voltage if the switch integrity is within operating norms, and activates the switch fault subroutine if the voltage is significantly lower than the pull up voltage. In some embodiments, the controller detects a change in voltage at the switch input under conditions in which the voltage is expected to fall to zero or nearly to zero after within a predetermined period if the switch integrity is within operating norms, and activates the switch fault subroutine if the voltage fails to fall to zero or nearly to zero within the predetermined period.
• the controller detects a change in voltage at the switch input under conditions where, the voltage should rise to a pull up voltage or nearly to the pull up voltage within a predetermined period if the switch integrity is within operating norms, and activates the switch fault subroutine if the voltage fails to rise to the pull up voltage or nearly to the pull up voltage within the predetermined period.
• a switch operated iontophoresis therapeutic agent delivery device comprising: (a) a power source; (b) first and second electrodes and reservoirs, at least one of the reservoirs containing the therapeutic agent; (c) a device switch, which provides a switch signal to a switch input of a device controller when operated by a user, the device controller, having said switch input operatively connected to the switch, whereby the controller receives the switch signal from the switch, the device controller being operatively connected to a power source that provides power to the first and second electrodes for delivering therapeutic agent to a patient; and (d) a switch integrity test subcircuit, which is configured to detect a fault in the switch and cause the controller to execute a switch fault subroutine when a fault is detected.
• the therapeutic agent is an opioid analgesic as described herein, such as fentanyl or sufentanil or a pharmaceutically acceptable salt, analog or derivative thereof.
• a method of switch fault detection in a user operated iontophoresis therapeutic agent delivery device comprising: (a) a power source; (b) first and second electrodes and reservoirs, at least one of the reservoirs containing the therapeutic agent; (c) a device switch connected to a switch input of a device controller; (d) the device controller comprising said switch input and configured to control power to the first and second electrodes, thereby controlling delivery of the therapeutic agent; and (e) a switch integrity test subcircuit, said method comprising said controller: (i) activating the switch integrity test subcircuit; detecting a voltage condition at the switch input; and (ii) activating a switch fault subroutine if the voltage condition at the switch input fails to meet one or more predetermined conditions.
• the switch fault subroutine includes, for example, activating a user alert, deactivating the device, or both.
• the methods of validating the operation of a switch and apparatus configured to validate the operation of a switch may include button sampling when monitoring the switch.
• monitoring the switch may generally include sequentially sampling a switch input, storing a window of sequential samples, and comparing a plurality of more recent sequential samples to a plurality of older sequential samples within the stored window of samples to detect the release event.
• Sequential sampling may refer to periodically sampling an input to the switch (e.g., the low or high side of the switch) at regular intervals, e.g., every 1 ms, 2 ms, 3 ms, 4 ms, 5 ms, 6 ms, 7 ms, 8 ms, 9 ms, 10 ms, etc.
• the plurality of more recent sequential samples may refer to 2 or more, 3 or more, 4 or more, 5 or more, etc., samples taken sequentially in time.
• the window of stored sequential samples may be a circular buffer, storing a rolling window of samples (e.g., any appropriate number of samples may be stored, with the most recent sample replacing the oldest sample in a continuous manner).
• a group of newer sequential samples may be compared to a group of older sequential samples and if the state change is made (e.g., when the older samples all indicate the switch is closed, and the newer samples all indicate the switch is open, a release event may be confirmed.
• monitoring the switch to determine a release event may include sequentially sampling a switch input, storing a window of sequential samples, and comparing three or more recent sequential samples to three or more older sequential samples within the stored window of samples to detect the release event, e.g., when the three or more recent samples indicate an open switch and the three or more older samples indicate a closed switch.
• the older samples and the more recent samples are generally non-overlapping.
• the failure mode may include suspending operation of the device, shutting the device off, or restarting the device.
• the failure mode may include preventing delivery of drug by the device, including (but not limited to) turning off the drug delivery device, and/or locking (e.g., inactivating) the drug delivery device.
• both digital and analog validation tests may be performed on the switch, typically during a period when the switch is reliable predicted to be in the "open" (inactivated) state.
• the inactivated state is known most reliably immediately or shortly (e.g. within micro- to mill- seconds) following user activation, as it may be impossible for a user to more quickly activate the switch immediately after one (or better yet, a series) of "pushes" or other activating input.
• a button activates the switch
• multiple times e.g., twice, within a predetermined activation period (e.g., two quick 'clicks' in succession)
• a predetermined activation period e.g., two quick 'clicks' in succession
• the period e.g., between about 8 ⁇ and 500 msec, between about 8 ⁇ and 400 msec, between about 8 ⁇ and 300 msec, between about 8 ⁇ and 200 msec; less than about 500 msec, less than about 400 msec, less than about 300 msec, less than about 200 msec, less than about 150 msec, less than about 100 msec, etc.
• both the analog and digital validation may be performed within this period, which may be referred to as a test period or test window.
• Analog validation of the switch typically means determining the actual voltage value of one or both sides of the switch and comparing them to one or more thresholds to confirm that they are within acceptable parameters.
• performing the analog validation of the switch may comprise performing an analog validation of the switch if the digital validation passes.
• Either or both digital and analog validation may include performing the analog validation using a dose switch circuit.
• the dosing switch circuit may be part of the processor/controller.
• method or apparatus may perform the digital validation and analog validation sequentially or in parallel.
• the digital validation step may be performed before the analog validation step; the analog validation step may be performed only if the digital validation passes (e.g., does not fail digital validation); the drug delivery apparatus may be re-started (e.g., the button sampling process may be re-started) if the digital validation of the switch fails.
• the digital validation generally includes a comparison of the logical values of digital validation lines from one or both sides of the switch to expected values based on the inputs from the power source (e.g., battery) to the switch. For example, digital validation may "fail" (e.g., failing the digital validation) if a secondary digital input on a first side of the switch does not match a primary digital input on the first side of the switch, or a secondary digital input on a second side of the switch does not match a primary digital input on the second side of the switch.
• the power source e.g., battery
• the primary digital input may be a first input line connected to the battery and the high side of the switch and the secondary digital input may be a second input line connected to the battery (e.g., a negative terminal of the battery) and the low side of the switch.
• the secondary digital input line may be a first digital test input line also connected on the high side of the switch.
• the analog validation may be performed using a first and second analog input line; the first analog test input line may be on the high side of the switch and the second analog test input line may be on the low side of the switch.
• Performing the digital validation may include failing the digital validation if a secondary digital input on a high side of the switch is low or if a secondary digital input on a low side of the switch is high.
• Performing the analog validation may include failing the analog validation if a measurement of a high side voltage is less than a first predetermined fraction (e.g., 90%, 85%, 80%, 75%, 70%, 65%, etc.) of a battery voltage for the drug delivery device, or a measurement of a low side voltage is greater than a second predetermined fraction (e.g., 90%, 85%, 80%, 75%, 70%, 65%, etc.) of the battery voltage.
• performing the analog validation may include failing the analog validation if a measurement of a high side voltage is less about 0.8 times a battery voltage for the drug delivery device, or a measurement of a low side voltage is greater than about 0.2 times the battery voltage.
• Performing the analog validation may include sequentially measuring a high side voltage and a low side voltage using an analog to digital converter (ADC) and failing the analog validation if the high side voltage is below a first predetermined threshold or the low side voltage is above a second predetermined threshold.
• ADC analog to digital converter
• digital validation of the switch may be performed before the analog validation of the switch.
• analog validation of the switch may be performed before the digital validation of the switch.
• a release event may include a second release of the switch within a predetermined time period.
• a release event may comprise a second release of the switch within less than about 400 msec, 300 msec, 200 msec, 100 msec, etc.
• a method of validating operation of a switch may include: monitoring the switch to determine a release event; performing a digital validation of the switch following the release event using a dose switch circuit and failing the digital validation if a secondary digital input on a high side of the switch is low or if a secondary digital input on a low side of the switch is high; performing an analog validation of the switch if the digital validation passes and failing the analog validation if a measurement of a high side voltage is less than a first predetermined fraction of a battery voltage for the drug delivery device or if a measurement of a low side voltage is greater than a second predetermined fraction of the battery voltage; and initiating a failure mode for the drug delivery device if the analog validation of the switch fails.
• a drug delivery device may include: a battery having a battery voltage; a switch configured to be activated by a user to deliver a dose of drug, the switch having a low voltage side and a high voltage side; a first input line on the high side and a second input line on the low side, wherein the first and second input lines are connected to the battery; a first analog test input line on the high side and a second analog test input line on the low side; a first digital test input line on the high side and a second digital test input line on the low side; and a controller configured to pe-form a digital validation of the switch following a release event of the switch and to perform an analog validation of the switch following the release event, wherein the controller is further configured to initiate a failure mode for the drug delivery device if the analog validation of the switch fails.
• any of these devices may include a circular buffer configured to store a plurality of sequential samples from an input line on the high voltage side of the switch, wherein the newest sample replaces the oldest sample.
• the controller may be configured determine a release event on the switch by being configured to sequentially sample an input line on the high voltage side of the switch, store a window of sequential samples, and compare a plurality of more recent sequential samples to a plurality of older sequential samples within the stored window of samples to detect the release event.
• the first and second analog test input lines may be connected to the controller, and further wherein the controller configured to fail the analog validation if a voltage on the first analog test line is below a first predetermined fraction of the battery voltage or if a voltage on the second analog test line is greater than a second predetermined fraction of the battery voltage.
• the first and second analog test input lines may be connected to the controller, and further wherein the controller configured to fail the analog validation if a voltage on the first analog test line is less about 0.8 times the battery voltage or if a voltage on the second analog test line is greater than about 0.2 time the battery voltage.
• the first and second digital test input lines may be connected to the controller, wherein the controller is configured to fail the digital validation if a value of the first digital test input line does not match a value of the first input line or if a value of the second digital test input line does not match a value of the second input line.
• the first and second digital test input lines may be connected to the controller, wherein the controller is configured to fail the digital validation if the first digital input line is low or if the second digital input line is high.
• the controller may be configured to perform the analog validation of the switch and the digital validation of the switch following a second release of the switch within less than about 500 msec (e.g., less than about 400 msec, less than about 300 msec, less than about 200 msec, less than about 100 msec, etc.).
• a drug delivery device adapted to validate the operation of a user-selectable activation switch to deliver a dose of drug may include: a battery having a battery voltage; a switch configured to be activated by a user to deliver a dose of drug, the switch having a low voltage side and a high voltage side; a first input line on the high side and a second input line on the low side, wherein the first and second input lines are connected to the battery; a first analog test input line on the high side and a second analog test input line on the low side, wherein the first and second analog test inputs lines are connected to a controller; and a first digital test input line on the high side and a second digital test input line on the low side, wherein the first and second digital test input lines are connected to the controller; wherein the controller is configured to perform a digital validation of the switch, following a second release of the switch within a predetermined time period, and to perform an analog validation of the switch following the second release of the switch within the predetermined time period
• any of the apparatuses described herein may be configured as are iontophoretic drug delivery devices adapted to validate the operation of a user-selectable activation switch to deliver a dose of drug using both digital and analog validation.
• These iontophoretic drug delivery devices may be configured (and particularly useful) for delivery of fentanyl or sufentanil.
• An iontophoretic drug delivery device may include: a battery having a battery voltage; a switch configured to be activated by a user to deliver a dose of drug, the switch having a low voltage side and a high voltage side; a first input line on the high side and a second input line on the low side, wherein the first and second input lines are connected to the battery; a first analog test input line on the high side and a second analog test input line on the low side; a first digital test input line on the high side and a second digital test input line on the low side; a controller configured to perform both a digital validation of the switch following a release event of the switch and to perform an analog validation of the switch following the release event, wherein the controller is further configured to initiate a failure mode for the drug delivery device if the analog validation of the switch fails.
• any of the apparatuses may include a circular buffer configured to store a plurality of sequential samples from an input line on the high voltage side of the switch, wherein the newest sample replaces the oldest sample. That is, the controller may sample and analyze the high side of the switch and start validation when the high side goes low (indicating a press event) and then return to high (indicating a release event).
• Any of the controllers described herein may be configured to sequentially sample an input line on the high voltage side of the switch, store a window of sequential samples, and compare a plurality of more recent sequential samples to a plurality of older sequential samples within the stored window of samples to detect the release event. Detecting a 'release event' may including detecting a preceding 'press event'.
• the first and second analog test input lines may be connected to the controller, and the controller may be configured to fail the analog validation if a voltage on the first analog test line is below a first predetermined fraction of the battery voltage or if a voltage on the second analog test line is greater than a second predetermined fraction of the battery voltage.
• the device of claim 1 wherein the first and second analog test input lines are connected to the controller, and further wherein the controller configured to fail the analog validation if a voltage on the first analog test line is less about 0.8 times the battery voltage or if a voltage on the second analog test line is greater than about 0.2 time the battery voltage.
• the first and second digital test input lines may be connected to the controller, and the controller may be configured to fail the digital validation if a value of the first digital test input line does not match a value of the first input line or if a value of the second digital test input line does not match a value of the second input line.
• the first and second digital test input lines may be connected to the controller, and the controller may be configured to fail the digital validation if the first digital input line is low or if the second digital input line is high.
• the controller may be further configured to perform the analog validation of the switch and the digital validation of the switch following a second release of the switch within less than about 100 msec.
• An iontophoretic drug delivery device adapted to validate the operation of a user-selectable activation switch to deliver a dose of drug using both digital and analog validation may include: a battery having a battery voltage; a switch configured to be activated by a user to deliver a dose of drug, the switch having a low voltage side and a high voltage side; a first input line on the high side and a second input line on the low side, wherein the first and second input lines are connected to the battery; a first analog test input line on the high side and a second analog test input line on the low side, wherein the first and second analog test inputs lines are connected to a controller; and a first digital test input line on the high side and a second digital test input line on the low side, wherein the first and second digital test input lines are connected to the controller; wherein the controller is configured to perform a digital validation of the switch, following a second release of the switch within a predetermined time period, and to perform an analog validation of the switch following the second release of
• any of the methods described herein may be methods of validating operation of a switch of an iontophoretic device using both digital and analog validation, wherein the switch is user-activated to deliver a dose of a drug (e.g., fentanyl or sufentanil) from a drug delivery device.
• a drug e.g., fentanyl or sufentanil
• any of these methods may be methods of validating operation of a switch of an iontophoretic device using both digital and analog validation for iontophoretic delivery of fentanyl or sufentanil.
• Such methods may include: monitoring the switch to determine a release event; performing a digital validation of the switch following the release event using a dose switch circuit and failing the digital validation if a secondary digital input on a high side of the switch is low or if a secondary digital input on a low side of the switch is high; performing an analog validation of the switch if the digital validation passes and failing the analog validation if a measurement of a high side voltage is less than a first predetermined fraction of a battery voltage for the drug delivery device or if a measurement of a low side voltage is greater than a second predetermined fraction of the battery voltage; and initiating a failure mode for the drug delivery device if the analog validation of the switch fails.
• monitoring the switch may include sequentially sampling a switch input, storing a window of sequential samples, and comparing a plurality of more recent sequential samples to a plurality of older sequential samples within the stored window of samples to detect the release event.
• Monitoring the switch may include sequentially sampling a switch input, storing a window of sequential samples, and comparing three or more recent sequential samples to three or more older sequential samples within the stored window of samples to detect the release event.
• initiating the failure mode may include turning off the delivery device, and/or inactivating the delivery device.
• any of these methods may include re-starting a button sampling process of the drug delivery device if the digital validation of the switch fails.
• Performing the digital validation may include failing the digital validation if a secondary digital input on a first side of the switch does not match a primary digital input on the first side of the switch, or a secondary digital input on a second side of the switch does not match a primary digital input on the second side of the switch; and/or failing the analog validation if a measurement of a high side voltage is less about 0.8 times a battery voltage for the drug delivery device, or a measurement of a low side voltage is greater than about 0.2 time the battery voltage.
• Performing the analog validation may include sequentially measuring a high side voltage and a low side voltage using an analog to digital converter (ADC) and failing the analog validation if the high side voltage is below a first predetermined threshold or the low side voltage is above a second predetermined threshold.
• ADC analog to digital converter
• a release event may include a second release of the switch within a predetermined time period.
• a release event may include a second release of the switch within less than about 100 msec.
• FIG. 1 illustrates an exemplary therapeutic agent delivery system
• FIG. 2 shows an embodiment of iontophoretic therapeutic agent delivery mechanism
• FIG. 3 shows an exemplary embodiment of a controller as connected to an activation switch
• FIG. 4 shows exemplary timing of an activation sequence
• FIG. 5 is an exemplary embodiment of a therapeutic agent delivery device having switch integrity testing
• FIG. 6 is an exemplary embodiment of a therapeutic agent delivery device with switch integrity testing
• FIG. 7 shows exemplary timing of an activation sequence with switch integrity testing
• FIG. 8 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a short interval switch grounding integrity test
• FIG. 9 shows signaling during the short interval switch grounding integrity test
• FIG. 10 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a short interval power switch integrity test
• FIG. 11 shows signaling during the short interval power switch integrity test
• FIG. 12 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a long interval analog switch grounding integrity test
• FIG. 13 shows signaling during the long interval analog switch grounding integrity test
• FIG. 14 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a long interval analog power switch integrity test
• FIG. 15 shows signaling during the long interval analog power switch integrity test
• FIG. 16 shows a flow chart of the dosing operation of an embodiment of a therapeutic agent delivery device with switch integrity testing
• FIG. 17 shows an exemplary embodiment of a switch integrity testing process.
• FIG. 18A shows a schematic illustration of one variation of a switch and control circuitry for performing both digital and analog validation.
• FIG. 18B is a table describing connections of the nodes from the example in FIG. 18 A.
• FIGS. 19A, 19B and 19C illustrates variations of the timing of dose switch activation sequences for an apparatus or method in which both analog and digital switch validation is performed within the predetermined time period immediately following a second manual switch actuation.
• FIGS. 19A, 19B and 19C show analog switch validation followed by digital switch validation, digital switch validation followed by analog validation and concurrent analog and digital switch validation, respectively.
• Embodiments described herein provide circuitry and methods for actively detecting faults and precursors to faults in devices, such as drug delivery devices, and more particularly iontophoretic drug delivery devices.
• a switch operated device such as a drug delivery device (e.g. a drug delivery pump, electrotransport device or iontophoresis device).
• the device comprises (a) a device switch configured to be operated by a user, which provides a switch signal to a switch input of a device controller when operated by a user; (b) the device controller, having said switch input operatively connected to the switch, and configured to receive the switch signal from the switch, the device controller being configured to actuate the device when the switch signal meets certain predetermined conditions; and (c) a switch integrity test subcircuit, which is configured to detect a fault or a precursor to a fault in the switch, whereby the controller executes a switch fault subroutine when a fault or a precursor to a fault is detected.
• the device When the device is an iontophoretic drug delivery device, the device further comprises other circuitry components, such as electrodes, one or more drug also called active reservoirs and one or more counter ion reservoirs which are capable of delivering drug to a patent in response to patient input.
• iontophoretic drug delivery device iontophoresis devices
• iontophoresis devices is illustrated below, though iontophoresis is well-characterized and is described in detail in US 7027859, for example.
• the switch integrity test subcircuit is configured to check for and detect a fault or a precursor to a fault in the switch or connecting circuitry.
• the act of checking for a fault or precursor to a fault includes setting a circuit condition to evoke a response in the circuit (for example, change in voltage, change in current) which is expected to fall within predetermined parameters if the circuit and its components are free of faults or precursors to faults.
• the switch integrity test subcircuit is configured to test for and detect at least one fault or precursor to a fault, such as a member of the group selected from the group consisting of contamination, shorts, (including intermittent short circuits), compromised circuit components (including malfunctioning resistors, integrated circuit pins or interfaces, and/or capacitors), etc.
• a fault or precursor to a fault such as a member of the group selected from the group consisting of contamination, shorts, (including intermittent short circuits), compromised circuit components (including malfunctioning resistors, integrated circuit pins or interfaces, and/or capacitors), etc.
• the switch integrity test subcircuit is configured to test for and detect a voltage or change in voltage in between a short between the switch input and ground or some intermediate voltage above ground (low voltage, V L ), a short between the switch input and a voltage pull up or some intermediate voltage below a pull up voltage (high voltage, V H ).
• the switch integrity test subcircuit is configured to test for and detect a voltage or change in voltage in between a short between the switch input and some intermediate voltage above ground (low voltage, V L ) and/or a short between the switch input and intermediate voltage below a pull up voltage (high voltage, V H )
• the switch integrity test subcircuit is configured to test for and detect a damaged circuit resistor, contamination (e.g.
• the switch integrity test subcircuit includes the controller and additional circuit components under control of the controller, which the controller is capable of placing in certain states to cause certain effects in the circuit.
• the controller can detect faults and precursors to faults in the device circuitry. It is a particular advantage of the instant device and methods that precursors to faults may be detected before they have manifested in such a way that their effects would be experienced by a patient.
• the switch integrity test subcircuit detects a fault or a precursor to a fault, it provides a fault signal to the controller, which in turn executes a switch faui subroutine, which includes, for example, at least one of: activating a user alert feature, logging detection of faults or precursors to faults, deactivating the device, or one or more combinations thereof.
• the user alert feature can include a variety of means to alert a user that operation of the system is considered compromised. Since the device is configured, in some embodiments, to detect precursors to faults, the device may activate the user alert even before a fault has been detected that would cause an effect that would be experienced by the patient.
• the user alert may be an indicator light, such as a colored light emitting diode
• LED an audible tone (such as a repeating "beep")
• a readable display such as a liquid crystal display (LCD)
• other user observable indicator such as a text message, email, voicemail, or other electronic message sent to a device that is observable by the patient, the caregiver or both, or combinations of two or more thereof.
• switch integrity test subcircuit detects a fault or a precursor to a fault, it provides a fault signal to the controller, which in turn executes a switch fault subroutine " is intended to indicate that the subsequent act of executing the switch fault subroutine happens as a consequence of (e.g., at the time of, or at some time after) the predicate event of detection of the fault or precursor to the fault.
• switch fault subroutine is intended to have analogous effect throughout this disclosure unless otherwise indicated.
• the controller can also log detection of faults or precursors to faults in memory, such as flash memory. In some such embodiments, the controller detects a certain type of fault, assigns it a fault code, and records the fault code in memory for retrieval at a later time.
• the controller may detect and record one of the following conditions: a low voltage at a point and under conditions where a high voltage would be expected for a normally operating circuit; a voltage at a point and under conditions that is higher or lower than the voltage that would be expected for a normally operating circuit; a voltage rise time that is longer or shorter than would be expected for a normally operating circuit; a voltage fall time that is longer or shorter than would be expected for a normally operating circuit; or combinations of two or more thereof.
• the switch fault subroutine includes deactivating the device.
• Methods of deactivating a device e.g. by irreversibly decoupling the voltage supply from the drug delivery circuit, shorting a power cell to ground, fusing a fusible link in the circuit, etc., are known.
• the circuitry and methods employed in United States Patent No. 7,027,859 which incorporated herein by reference, especially those recited between line 65 of column 6 and line 12 of column 8 of United States Patent No. 7,027,859 (and the accompanying figures) may be adapted to disable the circuit when the controller detects a voltage or current, or change thereof, that is outside of predetermined parameters.
• devices and methods taught herein will be capable of performing two or more of the functions of activating a user alert feature (e.g. activating a light and/or audible sound), logging the detected fault or precursor to a fault, and/or deactivating a device.
• the devices and methods taught herein are capable of activating a user alert feature, deactivating the device and optionally logging the detected fault or precursor to a fault.
• the controller is configured to measure a voltage or a rate of change of voltage at the switch input and execute the switch fault subroutine when the voltage or rate of change of voltage at the switch input fails to meet one or more predetermined parameters.
• the device is an iontophoresis delivery device comprising first and second electrodes and reservoirs, at least one of the reservoirs containing therapeutic agent to be delivered by iontophoresis. It is to be understood that the terms “higher” and “lower” are relative. Especially in embodiments in which the device is capable of detecting and responding to precursors to faults, the terms “higher” and “lower” may express deviations of as little as 10%, 5%, 2% or 1% of the expected values.
• a voltage that is higher than expected may be greater than from 10-200 mV, 10-100 mV, 10-50 mV, 20-200 mV, 20-100 mV, 20-50 mV, 50-200 mV, 50-100 mV, or 100-200 mV higher than the nominal voltage expected at the point and under the conditions tested.
• the "higher" voltage may be greater than 10 mV, 20 mV, 50 mV, 75 mV, 100 mV, 125 mV, 150 mV, 175 mV, 200 mV or 250 mV than would be expected at the same point under the conditions tested.
• a voltage that is lower than expected may be at least from 10-200 mV, 10-100 mV, 10-50 mV, 20-200 mV, 20-100 mV, 20-50 raV, 50-200 mV, 50-100 mV, or 100-200 mV lower than the voltage expected at the point and under the conditions tested.
• the "lower" voltage may be at least 10 mV, 20 mV, 50 mV, 75 mV, 100 mV, 125 mV, 150 mV, 175 mV, 200 mV or 250 mV less than would be expected at the same point under the conditions tested.
• Voltage rise and fall times may be characterized in the amount of time necessary (e.g., measured in ms or ⁇ ) for a point under a condition tested to achieve an expected voltage state. In terms of rise or fall times, the difference in rise or fall time from the expected rise or fall time may be as little as 1 ms or as much as 20 ms, e.g. 1, 2, 5, 10, 12.5, 15 or 20 ms, depending upon the point tested under the particular conditions. Voltage and current rise times may also be characterized by measuring a change in voltage or current between two selected time points and comparing them to the change in voltage or current that would be expected for a normally operating circuit at the point and under the condition tested.
• the device is capable of detecting subtle differences in circuit states - whether voltages, currents, changes in voltages or changes in currents. These subtle changes may indicate that the circuit board has been contaminated with one or more contaminants, is experiencing intermittent shorts between circuit components, has one or more compromised circuit components, or combinations thereof. Such embodiments permit the device to identify precursors to faults before they manifest as circuit faults that can affect delivery of a drug and in particular before they are noticed by, or affect, a patient.
• the predetermined conditions for actuating the device include the user activating the switch at least two times within a predetermined period of time. This feature permits the device to distinguish between purposeful activation of the switch by a user (patient or caregiver, preferably a patient) and spurious or accidental button pushes, e.g. those that occur during shipping or storage, those that occur from contamination, or those that may accidentally occur during placement of the device on the patient or during movement of the patient after the device has been applied to the patient. Activation of the switch by multiple button pushes or the like is described with reference to the figures herein.
• the time between button pushes - which is typically on the order of at least a few hundred milliseconds (ms) - affords one time window during which the device controller can actively test the switch circuit.
• the device is configured such that the device will initiate drug delivery when it receives two distinct button pushes of a predetermined separation in time - e.g. on the order of 100 - 400 ms, preferably about 300 ms.
• the controller can actively set certain circuit parameters (using the switch integrity test subcircuit), test voltages or changes in voltages at certain points and compare them to predetermined values that are indicative of what a normally operating circuit - i.e.
• the controller may set a switch input to a low state and remove a high supply voltage (V DD ), then check whether the switch input achieves a true low (expected) of 0 mV above the low supply voltage (V ss e.g., ground or some voltage above ground), or if it fails to achieve such a true low (indicating a fault or precursor to a fault) of at least 5 mV to at least 250 mV above V ss (e.g. at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 200, 225 or 250 mV above V S s). If a fault or precursor to a fault is detected, the device controller will then initiate a switch fault subroutine, as described elsewhere herein.
• V DD refers to any predetermined high voltage (V H ), and need not be the highest voltage available from the power supply.
• V ss refers to any predetermined low voltage (V L ) and need not indicate "ground”.
• V H predetermined high voltage
• V ss predetermined low voltage
• V L predetermined low voltage
• one advantage of the device and method described herein is that intermediate voltages may be used to test switch integrity, which allows for detection of spurious voltages that indicate contaminants (e.g. humidity, particulates, corrosion, etc.) and other faults and precursors to faults.
• the precise values of V DD and Vss are selected by the artisan during device design.
• the controller may set a switch input to a V DD (e.g. a value of from 2 V to 15 V, such as 5 V or 10 V) and connect the switch input to V ss (e.g. a value of 0 V to 1 V above ground), then check whether the switch input achieves V D D (as expected), or if it fails to achieve V DD
• V DD e.g. a value of from 2 V to 15 V, such as 5 V or 10 V
• V ss e.g. a value of 0 V to 1 V above ground
• the switch input is pulled up to V DD when the switch is open and the switch input is V ss when the switch is closed.
• V DD when the switch is open
• V ss when the switch is closed.
• Other configurations are possible.
• the switch input could be biased to V S s, meaning that upon a button push the switch input would be pulled high.
• the person of skill in the art will recognize that other configurations, including those requiring three, four or more sequential button pushes may be employed, though in general the inventors consider two to be sufficient for most purposes.
• Some embodiments described herein provide a method of switch fault detection in a switch operated device, said device comprising: (a) a device switch connected to a switch input of a device controller; (b) the device controller comprising said switch input; and (c) a switch integrity test subcircuit, said method comprising said controller: (i) activating the switch integrity test subcircuit; (ii) detecting a voltage condition at the switch input; and (iii) activating a switch fault subroutine if the voltage condition at the switch input fails to meet one or more predetermined conditions.
• the steps of activating the switch integrity test subcircuit and detecting a voltage condition at the switch input are executed continuously or periodically throughout operation of the device.
• a method may include digital or analog testing.
• Digital testing is relatively fast and is well-suited to performance during the test period between button pushes.
• Analog testing may be either fast or slow, depending upon how many data points are collected.
• Analog testing may be, and in some embodiments is, more sensitive and is well-adapted for detection of very subtle deviations from expected device parameters which are symptomatic of precursors to faults.
• Fast analog testing is well-suited for detection after any button bounce or anything (any voltage signal) that looks like (could be interpreted by the controller as) a button push.
• Analog testing is also well-suited for the period when drug is being delivered to a patient (that is after the second button press in the case where the device is activated by two distinct button presses) or even during the period between drug delivery intervals (that is when the device is still attached to the patient but is not currently delivering drug).
• the device may administer a very small amount of current for a brief period of time (e.g. 500 ms to 10 seconds, more preferably 500 ms to 5 seconds, even more preferably 500 ms to 1 second) during which time the controller carries out its active checking.
• analog checking is very sensitive and may detect subtle changes in circuit properties before they develop into full-fledged faults, thus permitting avoidance of untoward events before they can manifest.
• testing may include a combination of digital and analog testing.
• a fast analog test is conducted after any button push (including detection by the controller of any voltage signal that it interprets as a button push) and/or a digital test is conducted after a second button push.
• a fast analog test is conducted after any button push (including detection by the controller of any voltage signal that it interprets as a button push) and a digital test is conducted after a second button push.
• a slow analog test is conducted in addition to the digital test sometime after the second button push.
• Some embodiments described herein provide a switch operated iontophoresis therapeutic agent delivery device, comprising: (a) a power source; (b) first and second electrodes and reservoirs, at least one of the reservoirs containing the therapeutic agent; (c) a device switch, which provides a switch signal to a switch input of a device controller when operated by a user; the device controller having said switch input operatively connected to the switch, whereby the controller receives the switch signal from the switch, the device controller being operatively connected to a power source that provides power to the first and second electrodes for delivering therapeutic agent to a patient; and (d) a switch integrity test subcircuit, which is configured to detect a fault in the switch and cause the controller to execute a switch fault subroutine when a fault is detected.
• the therapeutic agent is fentanyl or sufentanil.
• fentanyl includes pharmaceutically acceptable salts of fentanyl, such as fentanyl hydrochloride and "sufentanil” includes pharmaceutically acceptable salts of sufentanil.
• Some embodiments described herein provide a method of switch fault detection in a user operated iontophoresis therapeutic agent delivery device, said device comprising: (a) a power source; (b) first and second electrodes and reservoirs, at least one of the reservoirs containing the therapeutic agent; (c) a device switch connected to a switch input of a device controller; (d) the device controller comprising said switch input and configured to control power to the first and second electrodes, thereby controlling delivery of the therapeutic agent; and (e) a switch integrity test subcircuit, said method comprising said controller: (i) activating the switch integrity test subcircuit; detecting a voltage condition at the switch input; and (ii) activating a switch fault subroutine if the voltage condition at the switch input fails to meet one or more predetermined conditions.
• the switch fault subroutine includes activating a user alert, deactivating the device, or both.
• the present invention relates generally to apparatus (e.g., electrical circuits) which are used to enhance the safety of electrophoretic drug delivery.
• Drugs having particular potential for use iontophoretic drug delivery include natural and synthetic narcotics.
• Representative of such substances are, without limitation, analgesic agents such as fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine.
• analgesic agents such as fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, bupre
• iontophoresis it is to be understood that when reference is made to a drug, unless otherwise stated, it is intended to include all pharmaceutically acceptable salts of the drug substance.
• fentanyl the inventors intend that term to include fentanyl salts that are suitable for delivery by iontophoresis, such as fentanyl hydrochloride.
• Other exemplary pharmaceutically acceptable salts will be apparent to the person having ordinary skill in the art.
• FIG. 1 illustrates an exemplary therapeutic agent delivery system.
• Therapeutic agent delivery system 100 comprises activation switch 102, controller 104 and therapeutic agent delivery mechanism 106.
• Activation switch 102 can be selected from a variety of switch types, such as push buttons switch, slide switches and rocker switches. In some embodiments, a push button switch is used. Though either a "momentary on” or “momentary off push button switch can be used, for the sake of clarity, a momentary on push button switch is given in each example.
• Controller 104 controls the administration of drugs to the patient as to the specific rate and amount a drug is dispensed. It can also be used to regulate the dosing interval.
• Controller 104 can also comprise a power source, such as a battery, or can simply regulate a power source external to the controller. Typically, the power source controlled by controller 104 is used to drive the delivery of the therapeutic agent through therapeutic agent delivery mechanism 106.
• Controller 104 can be implemented in a number of ways known in the art. It can comprise a microprocessor and memory containing instructions. Alternatively, it can comprise an appropriately programmed field- programmable gate array (FPGA). It can be implemented in discreet logic or in an application specific integrated circuit (ASIC).
• FPGA field- programmable gate array
• Therapeutic agent delivery mechanism 106 can be selected from a variety of dosing mechanisms including iontophoresis and IV-line pumps. In the former case, a small electric charge which is controlled by controller 104 is used to deliver a drug through a patient's skin. In the latter case, the controller 104 controls a pump which introduces the drug into an intravenous line.
• the examples herein refer to an iontophoretic drug dispenser.
• FIG. 2 shows an embodiment of iontophoretic therapeutic agent delivery mechanism.
• Iontophoretic therapeutic agent delivery mechanism 200 comprises active electrode 202, active reservoir 204, return electrode 212, counter ion reservoir 214. Active electrode 202 and return electrode 212 are electrically coupled to controller 104.
• Iontophoretic therapeutic delivery agent delivery mechanism 200 often takes the form of a patch which is attached to the skin of a patient (220).
• Active reservoir 204 contains ionic therapeutic agent 206, which can be a drug, medicament or other therapeutic agent as described herein and has the same polarity as the active electrode.
• Counter ion reservoir 214 contains counter ion agent 216, which is an ionic agent of the opposite polarity as the ionic therapeutic agent which can be saline or an electrolyte.
• iontophoretic therapeutic delivery mechanism 200 can further comprise additional active and/or counter ion reservoirs.
• controller 104 applies a voltage across active electrode 202 and return electrode 212, the patient's body completes a circuit. The electric field generated in this fashion conducts ionic therapeutic agent 206 from active reservoir 204 into the patient.
• controller 104 comprises power supply 240 which can be a battery. In other embodiments controller 104 controls an external power source.
• Therapeutic agent delivery mechanism 200 often comprises a biocompatible material, such as textiles or polymers, which are well known in the art as well as an adhesive for attaching it to a patient's skin.
• controller 104 and iontophoretic therapeutic agent delivery mechanism 200 are assembled together at the time of application of the therapeutic agent. This packaging permits ready application and insures the integrity of the therapeutic agent, but can also introduce addition points of failure of the delivery device.
• Therapeutic agent delivery system 100 is often used in circumstances which allow a patient to self- administer drug.
• an analgesic agent such as fentanyl or sufentanil, especially in form of a hydrochloride or other deliverable salt
• a patient can self-administer the analgesic agent whenever he feels pain, or whenever the patient's pain exceeds the patient's pain tolerance threshold.
• controller 104 Numerous safeguards and safety features are incorporated into controller 104, in order to ensure the patient's safety.
• the device may be configured to take into account the varying resistance of the patient's skin among other elements in the circuit.
• controller 104 can regulate the amount of current delivered to the patient in order to permit consistent delivery of the therapeutic agent, by monitoring the current (e.g., by measuring the voltage across a current sensing resistor) and adjusting the voltage up or down accordingly.
• the condition of the voltage supply prevents proper operation (e.g., weak battery)
• the device can shut down.
• Controller 104 upon activation can administer a single dose at the prescribed rate. To prevent inadvertent dosing, controller 104 can require the patient to activate activation switch 102 twice within a predetermined interval. As previously described, a predetermined test period interval can be used to insure that a single switch activation attempt by the patient is not incorrectly interpreted as two switch activation attempts. As described herein, this test period interval provides one convenient period during which a device as described herein can detect and respond to a fault or a precursor to a fault, e.g. using an analog or digital fault checking method.
• FIG. 3 shows an exemplary embodiment of a controller as connected to an activation switch.
• Activation switch 302 is shown as a push button momentary “on” switch and is coupled to the ground plane and to controller 300 through switch input 308.
• Controller 300 comprises pull up resistor 304 and control circuit 306.
• Pull up resistor 304 is coupled to a supply voltage V DD and switch input 308.
• Control circuit 306 is also coupled to switch input 308.
• the activation switch 302 When the activation switch 302 is closed, it pulls the voltage at switch input 308 down to ground.
• V DD V ss and ground
• V H any predetermined logic level high
• V S s or ground any predetermined logic level low
• V L any predetermined logic level low
• the logic high level is an intermediate voltage below VQD and/or the logic low level is some intermediate voltage above ground.
• the logic high level is an intermediate voltage below V DD and the logic low level is some intermediate voltage above ground.
• V H the logic high
• V L the logic low
• V H below V D D and/or V L above ground (or V ss ) permits the detection of indeterminate voltage signals that arise out of contamination, corrosion or other faults and precursors to faults.
• FIG. 4 shows exemplary timing of an activation sequence.
• Trace 400 shows a plot of voltage at the switch input as a function of time.
• the push button is depressed causing the voltage at switch input 308 to drop to the ground potential.
• the push button is released causing the voltage at switch input 308 to return to the supply voltage level.
• controller 300 enforces a predetermined minimum time interval 406 and a predetermined maximum time interval 412 between the release of the button after the first button press and the second pressing of the button. Should a button press occur before predetermined minimum time interval 406 has elapsed, it is ignored, as during this period it is not clear as to whether a second button press was intended or not.
• This interval is long enough to avoid an accidental reading, but sufficiently short that an average patient would have a difficult time pressing the button faster than the predetermined minimum time interval.
• Exemplary predetermined minimum time intervals are given in the overview discussed above.
• a second button press occurs, followed by a button release at time 410.
• controller 300 accepts the sequence as a valid activation sequence and the delivery of the therapeutic agent can begin, provided the second button press is completed before the predetermined maximum time interval has elapsed, for example within 3 seconds. This ensures that an accidental first button press does not leave the therapeutic agent delivery device armed so a second accidental button press could activate the delivery of the therapeutic agent.
• controller 300 can also incorporate logic and/or circuitry which prevent over-dosing of the therapeutic agent as well as prevent the dispensing of the therapeutic agent after a predetermined lifetime.
• logic and circuitry are described for instance in US 7027859, which is incorporated by reference in its entirety, especially as described elsewhere herein.
• V DD and V S s are used for illustrative purposes in FIG. 4, any logical high (V H ) can be used instead of V DD and any logical low (V L ) can be used instead of V ss .
• V H ⁇ V DD or V L > V ss In some embodiments V H ⁇ V DD and V L > Vss.
• controller 300 can detect whether there is a short (including an intermittent short) between switch 302 and either the ground plane or a power supply trace, which can result from contamination or corrosion.
• the short circuit can be a "hard" short or an intermittent short. Shorts, including intermittent shorts, can be caused by, for example, corrosion or contamination on the circuit. The corrosion or contamination can provide an electrical pathway, which may be continuous or spurious.
• controller 300 can detect whether there is damage to the switch input, which could be an integrated circuit pin or integrated circuit interface pad. A short due to contamination or corrosion, especially an intermittent short, may not necessarily cause the device to malfunction per se.
• the controller will detect intermittent shorts such as those described and initiate a suitable switch fault subroutine, as described herein.
• the switch fault subroutine may include setting one or more suitable user alerts (e.g. and audible tone or a visible indicator) and/or disabling the device (e.g. by disconnecting the power supply from the electrodes).
• FIG. 5 is an exemplary embodiment of a therapeutic agent delivery device embodying switch integrity testing.
• controller 510 comprises control logic 306, pull up resistor 304, and switch input 308.
• Controller 510 further comprises a switch integrity test subcircuit comprising switch 502 (which can be used to electrically decouple pull up resistor 304 from switch input 308), switch integrity test output 506 and integrity test sublogic 512 within control logic 306.
• Switch integrity test subcircuit is activated when switch integrity testing is performed.
• Integrity test sublogic 512 is configured to open switch 502 and set switch integrity output 506 to a predetermined voltage or sequence of voltages in accordance with a particular switch integrity test.
• switch integrity test output 506 can be implemented with a general purpose I/O port or an analog input pin.
• Switch integrity test output 506 is coupled to switch input 308 with resistor 504 which generally has a high resistance (e.g., 1 ⁇ ).
• Switch integrity test output 506 can be left floating, can provide a high supply voltage (V DD ) or can provide a low supply voltage (V ss ) (e.g., ground potential).
• V DD high supply voltage
• V ss low supply voltage
• switch 502 is opened electrically, decoupling pull up resistor 304 from switch input 308.
• switch integrity test output 506 provides a high supply voltage or a low supply voltage. Greater detail is given in the following description.
• FIG. 6 is an exemplary embodiment of a therapeutic agent delivery device with switch integrity testing. More specifically, controller 510 and more specifically integrity sublogic 512 (not shown) comprises switch 604 and switch 606 which are controlled by control logic 602. When switch 604 and switch 606 are open switch integrity test output 506 is left floating.
• switch integrity test output 506 When switch 604 is closed and switch 606 is open, switch integrity test output 506 provides a high supply voltage. When switch 604 is open and switch 606 is closed, switch integrity test output 506 provides a low supply voltage.
• V DD and ground are used for illustrative purposes in FIG. 6, any logical high (V H ) can be used instead of V DD and any logical low (V L ) can be used instead of ground. In some embodiments V H ⁇ V DD or V L > ground. In some embodiments V H ⁇ V D D and V L > ground.
• a variety of tests can be performed in this configuration.
• switch 302 is ignored until predetermined minimum time interval 406 has elapsed, during this period the integrity of switch 302 and its interfaces can be tested.
• a short test e.g. a fast analog test or a digital test
• a fast analog test is performed.
• time span 702 Depicted in FIG. 7 is time span 702 which is the time a short test can be performed.
• V H logical high
• V L logical low
• V H ⁇ VDD or V L > Vss- V H ⁇ V DD and V L > Vss
• FIG. 8 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a short interval switch grounding integrity test.
• switch integrity test output 506 is forced from a high supply voltage state to a low supply voltage state, depicted in FIG. 8 as grounding resistor 504. Additionally switch 502 is opened during the test.
• resistor 504 acts as a pull down resistor causing the voltage at switch input 308 to drop from V DD to V S s- The rate at which the voltage falls is based on the resistance-capacitance ("RC) time constant.
• the resistance in the circuit is furnished by resistor 504 and the capacitance is the capacitance inherent in switch input 308 and circuitry.
• controller 510 is implemented in an ASIC mounted to a printed circuit board (PCB), metal traces in the PCB, interface pins, balls or lands in the ASIC package can be major sources of capacitance. Due to experimentation, a nominal capacitance of controller 510 can be determined. Any deviation in the observed decay rate of the voltage seen at switch input 308 can result from resistor 504 being bad, contamination, shorts, open circuits ("opens"), missing or bad PCB traces, or a bad ASIC interface. For example, electrostatic discharge (ESD) during manufacturing, packaging, storage or use could damage the ASIC interface.
• ESD electrostatic discharge
• V H any logical high
• V L any logical low
• FIG. 9 shows signaling during the short interval switch grounding integrity test.
• Signal trace 902 is the signal from integrity switch test output 506 which initially begins at V DD and drops abruptly to V ss .
• Signal trace 904 is the signal observed at switch input 308 for a "good" therapeutic agent delivery device. After predetermined time interval 910 has elapsed after the drop in the voltage of integrity switch test output 506, the signal has decayed to a known value as indicated by arrow 912.
• V DD and V ss are used for illustrative purposes in FIG. 9, any logical high (V H ) can be used instead of V DD and any logical low (V L ) can be used instead of Vss- In some embodiments V H ⁇ V D D or V L > V S s- In some embodiments V H ⁇ V DD and V L > V S s.
• FIG. 10 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a short interval power switch integrity test.
• switch integrity test output 506 is forced from a low supply voltage state to a high supply voltage state, depicted in FIG. 10.
• resistor 504 acts as a pull up resistor causing the voltage at switch input 308 to rise from Vss to V DD .
• the rate at which the voltage rises is based on the RC time constant, similar to that described above for the short interval switch grounding integrity test.
• V H any logical high
• V L any logical low
• FIG. 11 shows signaling during the short interval power switch integrity test.
• the signal is logically complementary to that depicted in FIG. 9.
• Signal trace 1102 is the signal from integrity switch test output 506 which initially begins at V ss and rises abruptly to V DD .
• Signal trace 1104 is the signal observed at switch input 308 for a "good" therapeutic agent delivery device. After predetermined time interval 1110 has elapsed after the drop in the voltage of integrity switch test output 506, the signal has risen to a known value as indicated by arrow 1112.
• V H any logical high
• V L any logical low
• FIG. 12 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during an analog switch grounding integrity test.
• the equivalent circuit configuration shown in FIG. 12 is essentially the same configuration as that depicted in FIG. 8.
• control logic 306 further comprises a means for measuring the voltage at switch input 308.
• the means for measuring voltage is analog to digital converter ("ADC") 1204, however other methods for measuring voltage can be implemented, such as the use of a set of comparator circuits in place of the ADC to measure the voltage level of the analog signal compared to a comparator threshold.
• ADC analog to digital converter
• switch integrity test output 506 is forced down to a low supply voltage state, so resistor 504 acts as a pull down resistor.
• FIG. 13 shows signaling during the long interval analog switch grounding integrity test. (Although reference is made to a long interval analog grounding integrity test, the test may be made short interval by adjusting the number of data points collected.)
• Signal trace 1302 is the signal from integrity switch test output 506 which initially begins at V DD and drops abruptly to V S s.
• Signal trace 1304 is the signal observed at switch input 308 for a "good" therapeutic agent delivery device.
• predetermined interval 1310 After predetermined time interval 1310 has elapsed after the drop in the voltage of integrity switch test output 506, the signal has decayed to its final value. Predetermined interval 1310 differs from predetermined interval 910 shown in FIG. 9. Because the objective of the short interval test is to measure the rate of decay, predetermined interval 910 should be short enough so that any change in the RC time constant would be observed. In contrast, predetermined interval 1310 should be long enough so that the signal observed at switch input 308 should have decayed to a steady state voltage regardless of the RC time constant (or at least within a reasonable range of RC time constants).
• Signal trace 1306 is the signal observed at switch input 308 for a therapeutic delivery agent when corruption or some other source causes a short between a high power supply and switch 302 and/or switch input 308.
• the discrepancy between the steady state voltage and V ss is indicated by arrow 1308.
• V DD and V ss are used for illustrative purposes in FIG. 13, any logical high (V H ) can be used instead of V DD and any logical low ( V L ) can be used instead of V S s-
• control logic 306 measures the voltage at switch input 308. If the steady state voltage exceeds a given threshold, a fault can be indicated by controller 510.
• a precursor to a fault can be indicated and appropriate action can be taken by controller 510.
• FIG. 14 shows an equivalent circuit configuration of therapeutic agent delivery device 500 during a long interval analog power switch integrity test.
• the equivalent circuit configuration shown in FIG. 14 is essentially the same configuration as that depicted in FIG. 10.
• control logic 306 further comprises a means for measuring the voltage at switch input 308.
• switch integrity test output 506 is forced up to a high supply voltage state, so resistor 504 acts as a pull up resistor.
• V H any logical high
• V L any logical low
• FIG. 15 shows signaling during the long interval analog power switch integrity test.
• Signal trace 1502 is the signal from integrity switch test output 506 which initially begins at V ss and rises abruptly to V DD .
• Signal trace 1504 is the signal observed at switch input 308 for a "good" therapeutic agent delivery device.
• predetermined time interval 1510 After predetermined time interval 1510 has elapsed after the rise in the voltage of integrity switch test output 506, the signal has risen to its final value.
• predetermined interval 1510 differs from predetermined interval 1110 shown in FIG. 11, for reasons similar to the difference between predetermined interval 1310 and predetermined interval 910.
• Signal trace 1506 is the signal observed at switch input 308 for a therapeutic delivery agent when corruption or some other source causes a short between a low power supply and switch 302 and/or switch input 308.
• the discrepancy between the steady state voltage and V DD is indicated by arrow 1508.
• V DD and V S s are used for illustrative purposes in FIG. 15, any logical high (VH) can be used instead of V DD and any logical low (V L ) can be used instead of Vss- In some embodiments VH ⁇ V DD or V L > Vss- In some embodiments V H ⁇ V DD and V L > V ss .
• control logic 306 measures the voltage at switch input 308. If the voltage differential between the steady state voltage and V DD exceeds a given threshold, a fault can be indicated by controller 510. Additionally or alternatively, if the voltage differential exceeds a second threshold a precursor to a fault can be indicated and appropriate action can be taken by controller 510.
• FIG. 16 shows a flow chart of the dosing operation of an embodiment of a therapeutic agent delivery device with switch integrity testing.
• the device waits for a button release. This corresponds to waiting for event 404 in FIG. 7.
• one or more short switch integrity tests can be performed such as those described above in FIGS. 8-1 1.
• the device waits for a second button release. After the button has been released, at step 1608, a determination is made as to whether the second button press has occurred within the predetermined minimum time interval. If it has not, the last button release is ignored and the device returns to step 1606 where it waits for another button release.
• step 1612 delivery of the therapeutic agent begins. (Although not specifically depicted in FIG. 16, it is to be understood that one or more switch integrity checks may be performed between step 1610 and step 1612, such as a digital switch integrity check or a fast analog integrity check.) Concurrently with delivery of therapeutic agent, the device can perform one or more optional long switch integrity tests at step 1614. . Concurrently, a determination is made at step 1616 as to whether a fault with sufficient severity to warrant the shutdown of the device has occurred. If so the device shuts down at step 1618.
• FIG. 17 shows exemplary embodiment of a switch integrity testing process.
• the flowchart shown is representative of typical switch integrity processes which be used in steps 1604 and/or step 1614.
• device 500 activates its switch integrity subcircuit. In the examples given above, this can include opening switch 502, setting the switch integrity test output to a predetermined voltage such as V DD or V ss and/or optionally powering on or activating ADC 1204 such as in the configurations shown in FIGS. 12 and 14. In some embodiments, the ADC circuitry could be powered off when not testing to save power.
• one or more predetermined voltage conditions are tested for. Examples of these conditions are described above in FIGS. 8- 15. For example, in the short tests described in FIGS.
• the voltage at switch input 308 is measured. If the measured voltage has risen or decayed to the expected voltage, a voltage condition is deemed to be detected. In another example, in the long tests described in FIGS. 12- 16, after a predetermined time interval has elapsed after the switch integrity test output is set to the predetermined voltage, the voltage at switch input 308 is measured. If a discrepancy exists between the predetermined voltage and the measured voltage then a voltage condition is deemed to be detected.
• the fault subroutine can take one or more courses of action depending on the severity of the fault or precursor to a fault. For example, the patient or care provider can be alerted by activating a user alert feature. As previously discussed, the user alert feature can include a variety of means to alert a user that operation of the system is considered compromised.
• the device is configured to detect precursors to faults, so the device may activate the user alert even before a fault has been detected that would cause an effect that would be experienced by the patient.
• the user alert may be an indicator light, such as a colored light emitting diode (LED), an audible tone (such as a repeating "beep"), a readable display (such as a liquid crystal display (LCD)), other user observable indicator, communications to an external monitoring device, (e.g., a wireless transmission to a central console) or combinations of two or more thereof.
• indicator light such as a colored light emitting diode (LED), an audible tone (such as a repeating "beep"), a readable display (such as a liquid crystal display (LCD)), other user observable indicator, communications to an external monitoring device, (e.g., a wireless transmission to a central console) or combinations of two or more thereof.
• the faults and precursors to faults can be logged in memory.
• the controller detects a certain type of fault, assigns it a fault code, and records the fault code in memory for retrieval at a later time.
• the controller may detect and record one of the following conditions: a low voltage at a point and under conditions where a high voltage would be expected for a normally operating circuit; a voltage at a point and under conditions that is higher or lower than the voltage that would be expected for a normally operating circuit; a voltage rise time that is longer or shorter than would be expected for a normally operating circuit; a voltage or current fall time that is longer or shorter than would be expected for a normally operating circuit; or combinations of two or more thereof.
• the logs can be retrieved in several ways, for example it may be retrieved by a removable memory medium such as flash memory, viewed by a care provider by one or more visual messages on a display device, or transmitted to an external monitoring device.
• the device when the faults have sufficient severity pose a risk to a patient, the device can be deactivated such as by irreversibly decoupling the voltage supply from the drug delivery circuit, shorting a power cell to ground, fusing a fusible link in the circuit, by means of software logic, etc., as described herein.
• the fault subroutine can perform a combination of the actions described. For example, initially, precursors to faults are logged, but as the severity of the potential faults increases, a user alert is issued. Finally, when potential faults become actual faults and the severity is sufficiently high, the device shuts down at step 1618.
• the switch integrity process can proceed to step 1710 where either the device prepares for the next test or prepares to end the final test.
• the device may set the switch integrity test output to another voltage.
• the switch integrity test output could be set to V DD so that when the grounding tests begins in step 1702 the switch integrity test output can be driven down to Vss to initiate the test. However, this can be minimized by proper selection of tests.
• the device can deactivate the switch integrity subcircuit, for example the switch integrity test output can be set to its non-test default state which can be either the high supply voltage or the low supply voltage. Alternatively, the switch integrity test output could be left floating. Additionally switch 502 is closed so that resistor 304 can resume its pull up function.
• FIG. 18A illustrates one example of a circuit description for a drug delivery device that performs both analog and digital switch validation.
• a normally-open switch e.g., a momentary-contact push-button switch (SWl) is located in the circuit.
• SWl momentary-contact push-button switch
• the SWl switch is located on the IT101 circuit board, and is referred to as the dose switch.
• Each side of the switch is directly connected to three separate lines on the circuit (IC), which contains the control logic.
• the Auxl, P0 and GPIO0 lines are on one side of the dose switch and Aux2, KP3, and GPI02 are on the other side of the dose switch. These connections allow the controller (e.g., "ITSIC") to confirm that the dose switch is operating properly. Any appropriate dose switch may be used.
• the dose switch may be a mechanical switch configured as a button having a round metal snap dome, with a characteristically short contact bounce. No electrical de-bouncing is required for such an example, although switches with electrical de-bouncing could be used.
• FIGS. 18A and 18B show the dose switch connection design and descriptions of nodes.
• the high side of the switch (“A") includes nodes for the first power input line (KPO), the first digital test input line (GPIO_0), the first analog test input line (AUX1).
• the low side of the switch (“B") includes nodes for the second power input line (KP3), the second digital test input line (GPIO_l), and the second analog test input line (AUX2).
• the battery (Vbat) is also shown connected to the KPO and KP3 lines, including pull-up resistors (RpuO and Rpu3).
• the analog and digital test input lines all connect to the controller
• ITSIC digital validation
• AUX1 and AUX2 analog validation
• Three separate techniques may provide redundancy and enable demonstration of the validation method to a high degree of certainty, particularly when all three are employed and integrated as part of the apparatus. Specifically, button sampling, analog switch validation, and digital switch validation may all be included.
• button sampling may be used to detect button pressing and release.
• button sampling may include the use series of sequential state tests to determine when the button is in a stable configuration (e.g., pressed or released) by comparing sequential samples taken over a short period of time. Rapid changes in the state indicate that the button is not in a stable ("pushed" or "released") state.
• button inputs may be sampled periodically, e.g., every n ms (e.g., where n may be 2 ms, 3 ms, 4 ms, 5 ms, 6 ms, 7 ms, 8 ms, 9 ms, 10 ms, between about 1-20 ms, 1-10 ms, 2-10 ms, etc.).
• the sampling frequency may provide responsiveness to user inputs.
• the sampled data may be buffered into a circular buffer that holds a predetermined number of samples (e.g., 4 samples, 5 samples, 6 samples, 7 samples, 8 samples, 9 samples, 10 samples, 11 samples, 12 samples, 13 samples, etc.).
• the most recent samples e.g., the four most recent samples
• the state of the button is determined (e.g., as open or closed) when all of the most recent samples (e.g., all four samples) are the same state. This distinguishes a stable button state from a mechanical switch bounce or electrical noise. If the buffer contains a mix of low and high sample values, the signal may be determined to be a result of switch bounce or electrical noise and the apparatus may ignore the signal.
• Press and release transitions may be detected, and upon each transition, the state of the buttons may be sampled (e.g., at a rate of approximately 50ms). For example, a release transition may be confirmed by detection of four depressed states flowed by four released states, and a press transition may be confirmed by the opposite sequence. If the button is sampled every 8 ms and 4 samples are examined within the rolling window, the result is approximately 65 ms of sampling time to identify a valid button state transition.
• Using two separate switch validation techniques/pathways may provide redundancy and enable demonstration of the validation to a high degree of certainty in a way that is surprisingly better than a single validation technique/path.
• the analog switch validation test and the digital switch validation test are both performed, or may both be performed; in some variations both tests are performed only when one of the test is performed first and passes (e.g., is true). For example, the analog switch validation may be performed only if the digital switch validation is true, or vice/versa.
• the controller typically controls and monitors the dose switch circuit using both digital and analog signals.
• An analog portion of the dose switch circuit may be used to monitor analog voltages on both sides of the dose switch (e.g., the high, "A", and low, "B", sides).
• a digital portion of the dose switch circuit may be used for switch bias control and digital monitoring on both sides of the switch.
• software may configure the keypad input pull-up KP0 and GPIO[l] to establish a Vbat bias across the switch 1802, as shown.
• KP3 and GPIO[0] may be used to monitor the digital state of the switch.
• An analog switch validation test may measure the voltage levels on both the high and low sides of the dose button switch in order to detect potential problems that could lead to erroneous switch readings.
• voltage on the high side of the switch will be slightly less than battery voltage, after accounting for the small voltage drop caused by the electronic components connected to the switch circuit.
• the voltage on the low side of the switch will be very close to ground. Some conditions, such as contamination or corrosion, can cause the high-side voltage to drop, or the low-side voltage to rise.
• the switch input may fall in a range of indeterminate digital logic level with respect to the digital switch input.
• a predetermined high-side threshold such as some predetermined high-side fraction of the battery voltage (e.g., 0.8 x battery voltage)
• some predetermined low- side threshold such as a predetermined low-side fraction of the battery voltage (e.g., 0.2 x battery voltage)
• the switch input may fall in a range of indeterminate digital logic level with respect to the digital switch input.
• a switch voltage in this range could result in erroneous switch readings, which could manifest as false button transitions that were not initiated by the user, and therefore improper dosage.
• An analog switch validation test may therefore detect a condition before the switch voltage levels reach the point where erroneous readings could occur.
• the analog switch validation test may be run when the switch is in its normally-open condition, so that the high- and low-side voltages can both be measured. Any change in the switch state while the test is running could cause the test to falsely fail due to measurement of the high-side voltage while the switch is closed. Since a user may press or release the button at any time, the apparatus may be configured to run the test in such a way to avoid interference with normal operation, e.g., allowing a button push, or more likely a pair of button pushes, at any time without interfering with the analog and/or digital switch validation.
• the apparatus and methods described herein may take advantage of the fact that there are mechanical and human limits on the minimum time between button presses, and thus the point where the switch state is known to be open with the greatest certainty is immediately following a detected release of the button.
• the analog and/or digital switch validation may be performed following one or more button pushing events, or more likely button release events.
• an analog switch validation test may be performed immediately following the second button release of a double-press that meets the criteria for a dose initiation sequence.
• An analog switch validation may use an analog-to-digital converter (ADC), e.g., part of the controller/processor (e.g., ITSIC), to make sequential measurements of the high-side voltage and the low-side voltage.
• ADC analog-to-digital converter
• an ADC may be configured to sample for 6.25 ms for each measurement. If the voltage on the high side of the switch is less than or equal to the high side predetermined threshold (e.g., 0.8 x battery voltage), or if the voltage on the low side is greater than or equal to the low side predetermined threshold (e.g., 0.2 x battery voltage), the test fails.
• the switch high and low limits may be calculated and stored each time the battery voltage is measured for a battery voltage test.
• a digital switch validation test is generally also performed by the apparatus and methods describe herein.
• a digital switch validation test may be similar in purpose to the analog switch validation test, but is generally simpler, faster, and coarser in its measurements.
• the test may use secondary digital inputs (e.g., GPIO[0] and GPIO[l] in FIGS. 18A and 18B), connected to each side of the dose switch 1802, to confirm the digital logic levels while the switch is open (e.g., button not depressed).
• These "secondary" digital inputs e.g., first and second digital test input lines
• the first (high side) digital input test line should have the same logical value as the first input line connected to the battery and the second (low side) digital input test line should have the same logical value as the second input line.
• the digital switch validation test may be run either before, during or after an analog switch validation test.
• the performance of the analog switch validation test may depend on a successful digital switch validation test, or vice versa.
• an analog switch validation test may be performed after a successful digital switch validation test following the second button release of a double-press that meets the criteria for a dose initiation sequence.
• the digital switch validation test fails, and the system may initiate a failure mode (e.g., a digital switch validation failure mode); if the secondary digital input on the high side of the switch is high, and if the secondary digital input on the low side of the switch is low, the digital switch validation test passes, and the system may then perform an analog switch validation, as described above. If the analog switch validation test fails, then the system may also initiate a failure mode (e.g., an analog switch validation failure mode).
• a failure mode e.g., a digital switch validation failure mode
• the failure mode may include locking the device (to prevent further activations), shutting the device down, restarting the device, issuing an alert/warning (e.g., buzzer, alarm, etc.), disconnecting the battery from the circuit, or some combination of these. For example, if the analog switch validation test fails, the apparatus may enter into an end of life mode.
• FIGS. 19A-19C illustrate variations on the timing of a dose switch activation sequence for an apparatus or method that is configured to perform both analog and digital switch validation tests.
• both the switch validation tests are performed.
• the analog switch validation (ASV) test is performed first, followed by the digital switch validation (DSV) test.
• the digital switch validation test may be performed if the analog switch validation test is good (e.g., if the high and low sides of the switch are within the acceptable voltage ranges set by the predetermined thresholds (e.g., > 0.8xVbat on the high side and ⁇ 0.2Vbat on the low side).
• Both the analog and the digital switch validation tests may be performed within a window of time following release of the switch (e.g., following the second release within a switching time period).
• the window of time may begin immediately or shortly after detecting the release of the switch and extend for a period of time during which it is impossible or highly unlikely that a subject could push the button again.
• the switch validation tests may be performed before the test period (test window) has ended (e.g., 500 ms, 400 ms, 300 ms, 200 ms, 150 ms, 100 ms, 50 ms, etc.).
• the digital switch validation (DSV) test is performed first, followed by the analog switch validation (ASV) test.
• the analog switch validation may be performed only if the digital switch validation passes (e.g., the high side is a logical 1 and/or matches the high-side voltage input from the first input line connected to the battery, and the low side is a logical 0 and/or matches the low-side voltage input from the opposite input line). If the digital switch validation does not pass, the device may enter a first failure mode (e.g., restarting, and/or incrementing a counter or flag indicating failure of the digital switch validation, shutting down, etc.).
• a first failure mode e.g., restarting, and/or incrementing a counter or flag indicating failure of the digital switch validation, shutting down, etc.
• the device may enter into a second failure mode (e.g., shutting the device down, restarting the device, issuing an alert/warning, disconnecting the battery from the circuit, or some combination of these).
• the first and second failure modes may be the same. In some variations, the first and second failure modes are different. For example, if the digital switch validation test fails, the software may ignore that dose request and remains in Ready mode (first failure mode), and if the analog switch validation test fails, the apparatus may enter into an end of life failure mode (EOL mode).
• the analog switch validation test is more sensitive (e.g., uses more sensitive circuitry) than the digital switch validation test. Passing the analog switch validation test may indicate that the circuitry is intact; failure of the analog switch validation test may indicate a failure of the circuitry. In such instances, failure of the analog switch validation test may therefore cause the apparatus to enter into EOL (end of life) mode. Passing the digital switch validation test may also (redundantly) indicate that the circuitry is intact, but failure of the digital switch validation test may not necessarily indicate failure of the circuitry. Failure of the digital switch validation test may also be a result of temporary electrical noise signals. Performing the analog switch validation test before the digital switch validation test may therefore prevent false positive failures of the digital switch validation test from disabling the system by entry to EOL mode.
• FIG. 19C illustrates another variation in which the analog and digital switch validation modes are performed at the same time, or approximately the same time, following the second release of the does switch detected during the allowable time period (e.g., the time period when to activations of the does switch indicate a dose is requested).
• first and second may be used herein to describe various features/elements, these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
• a numeric value may have a value that is +/- 0.1% of the stated value (or range of values), +/- 1% of the stated value (or range of values), +/- 2% of the stated value (or range of values), +/- 5% of the stated value (or range of values), +/- 10% of the stated value (or range of values), etc. Any numerical range recited herein is intended to include all sub-ranges subsumed therein.

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• Primary Health Care (AREA)
• Neurology (AREA)
• Anesthesiology (AREA)
• Vascular Medicine (AREA)
• Hematology (AREA)
• Dermatology (AREA)
• Electrotherapy Devices (AREA)
• Infusion, Injection, And Reservoir Apparatuses (AREA)
• Dental Tools And Instruments Or Auxiliary Dental Instruments (AREA)

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• 2015
  • 2015-06-03 EP EP15803693.9A patent/EP3151905A4/en not_active Withdrawn
  • 2015-06-03 JP JP2016571154A patent/JP2017518111A/ja active Pending
  • 2015-06-03 KR KR1020167036739A patent/KR20170016890A/ko unknown
  • 2015-06-03 MX MX2016015453A patent/MX2016015453A/es unknown
  • 2015-06-03 SG SG11201609567WA patent/SG11201609567WA/en unknown
  • 2015-06-03 CA CA2949709A patent/CA2949709A1/en not_active Abandoned
  • 2015-06-03 WO PCT/US2015/033990 patent/WO2015187834A1/en active Application Filing
  • 2015-06-03 AU AU2015271708A patent/AU2015271708A1/en not_active Abandoned
  • 2015-06-03 CN CN201580041791.5A patent/CN106573136A/zh active Pending
  • 2015-06-03 RU RU2016152271A patent/RU2016152271A/ru not_active Application Discontinuation
• 2016
  • 2016-11-17 IL IL249023A patent/IL249023A0/en unknown

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