Ready-to-use detector

Abstract

Systems and methods for detecting the temperature of a pharmaceutical product and indicating whether the pharmaceutical product is ready to be used after a specified amount of time has elapsed are provided herein. A detector provided herein is configured to be attached to the pharmaceutical product containing an active pharmaceutical ingredient (API) therein, and includes: a temperature sensor configured to detect a temperature of the pharmaceutical product; at least one timer configured to begin measuring an elapse of time if the temperature of the drug product detected by the temperature sensor reaches or exceeds a breakthrough temperature; and at least one indicator configured to generate an indication that the pharmaceutical product is ready to be used if a specified amount of time has elapsed on the at least one timer.

Description

Technical Field

[0001] The present disclosure relates generally to detectors for pharmaceutical products, and particularly to detectors that determine and indicate when a pharmaceutical product is ready to be used. Background Art

[0002] Drug products are accompanied by instructions for use (IFUs) on the label and / or package insert that inform the user how and when to use the drug product. For example, a drug product may contain an active pharmaceutical ingredient (API) that needs to be stored in a cool environment (e.g., a refrigerator, freezer, etc.) until the API is consumed to maintain the effectiveness, sterility, and / or physical form of the API. The duration that the API can be kept outside of a controlled cooling environment varies from API to API. The IFU informs the user of the duration that the API must be placed in the ambient environment (e.g., outside the refrigerator) before using the API, as well as the maximum amount of time that the API can be kept outside the refrigerator before it expires.

[0003] Drug delivery performance is highly dependent on the temperature-sensitive formulation properties of API, such as viscosity and density. For example, API can be injected, orally ingested / consumed or inhaled (for example, manually by the user or using an automatic syringe). When injecting drugs by needle, injection force (for example, for manual injection) and injection time (for example, for mechanical assisted delivery, such as an automatic syringe) are highly dependent on formulation temperature. API temperature is inversely proportional to viscosity, injection time and injection force, so that lower temperatures lead to higher viscosity, longer injection time and require greater injection force. Therefore, it is necessary for drug products (for example, API) to stand for a certain duration in the surrounding environment outside a controlled cooling environment to reduce viscosity, increase temperature, thereby reducing the force and injection time required for injecting API (manually or by using an automatic syringe). Summary of the invention

[0004] Systems, devices, and methods are provided herein for determining and indicating when a drug product is ready to be used. The detectors described herein can detect the temperature of a drug product, measure the time lapse once a breakthrough temperature is reached or exceeded, and indicate whether the drug product is ready to be used after a specified amount of time has passed.

[0005] As mentioned above, drug products are traditionally accompanied by instructions for use (IFU) on product labels and / or package inserts, which inform users how / when to use the drug products. For example, a drug product may contain an active pharmaceutical ingredient (API), which needs to be stored in a cool controlled environment (e.g., refrigerator, freezer, etc.) until the consumption time to maintain the stability of the API. The IFU informs the user of the minimum and maximum duration that the drug product containing the API must be left at ambient temperature (e.g., room temperature) before using the drug product. The API may need to be left at room temperature, at least because the drug delivery performance (e.g., injection time and / or injection force) may be highly dependent on the viscosity of the fluid, wherein the viscosity is negatively correlated with the temperature of the API. Therefore, at cooler temperatures, the viscosity of the API is higher, which results in an extended injection time and a larger required injection force that may exceed the user's and / or the ability of the automatic injector. Although the waiting time is informed to the user in the IFU, as described in more detail below, the waiting time observed by the user before using the drug product is usually inefficient, inaccurate, and ignored by the user.

[0006] For example, the user may not read the IFU material, but will roughly estimate the duration that the drug product must sit outside the controlled cooling environment before using the drug product. In some embodiments, the user may not follow the IFU or medical professional instructions at all, but may attempt to use (e.g., inject) the API of the drug product without waiting any duration after taking the drug product out of the controlled cooling environment. In some cases, the user may forget about the drug product after taking it out of the controlled cooling environment, and leave the product in the ambient environment for a duration that exceeds the maximum duration that the product can be left in the ambient environment, thereby causing the API to expire.

[0007] Additionally, the duration that a drug product may need to stand outside a cooling environment may vary based on the temperature of the environment in which the drug product is placed. For example, in the case where a drug product is placed in an environment warmer than the ambient temperature, less time may be required to reach the appropriate use temperature. On the other hand, in the case where a drug product is placed in an environment cooler than the ambient temperature (but still above the temperature range of the controlled cooling environment), more time may be required to reach the appropriate use temperature. In some cases, a drug product may never reach the desired use temperature, or may require an excessive amount of time to reach the desired use temperature. Additionally, a user may use multiple different drug products every day, and each product may require a different duration to warm up to the appropriate use temperature; or the appropriate use temperature may be different for each product. Therefore, a user may incorrectly associate a waiting time with a given drug product and use their drug product incorrectly.

[0008] Improper use of API may cause many problems for the user. For example, when the API is injected into the user, the injection time may be extended when the API has not yet reached the appropriate use temperature. As mentioned above, this is caused by the higher viscosity of the API, which is negatively correlated with the temperature of the API. In some cases, when the API is not at the appropriate use temperature, the syringe may not be able to fully inject (or completely fail to inject) the API. For example, low temperature and high viscosity may require a larger injection force that exceeds the user's ability, or exceed the maximum spring force that can be applied by the spring of the automatic injector when injecting the API with an automatic injector. In addition, the injection of an API that has not yet reached the appropriate temperature may cause discomfort and pain to the user at least at the injection site. Pain may be caused at least by the low temperature of the API and / or the high viscosity of the fluid, which may not allow the fluid to disperse after injection. Additionally, when the drug product is left outside the controlled cooling environment for more than the maximum duration informed (for example, the user forgets the product after taking the product out of the cooling environment), the drug product may lose its efficacy, and worse is expired. For example, the sterility of the drug product may be compromised and the physical form of the API may be compromised, rendering the drug product unsuitable for use.

[0009] Provided herein is a detector configured to be attached to a pharmaceutical product. The detector is configured to automatically detect the temperature of the pharmaceutical product, measure one or more time lapses once one or more breakthrough temperatures are reached or exceeded, and indicate whether the pharmaceutical product is ready to be used after a specified amount of time. The detector can mitigate any risk of user confusion and more effectively inform the user when the pharmaceutical product is ready to be used by tracking both time and temperature. The pharmaceutical product may include, for example, a syringe (e.g., an automatic syringe, a syringe (syringe), a manual syringe, etc.) and a container (e.g., a vial, a bottle, a cartridge, etc.) that holds or is configured to hold an active pharmaceutical ingredient (API) (e.g., a drug, a medicament, an antibiotic, a vaccine, a drug, etc.).

[0010] In some embodiments, a detector is provided that is configured to be attached to a drug product containing an active pharmaceutical ingredient (API) therein, the detector comprising: a temperature sensor configured to detect a temperature of the drug product; at least one timer configured to begin measuring the passage of time when the temperature of the drug product detected by the temperature sensor reaches or exceeds a breakthrough temperature; and at least one indicator configured to generate an indication that the drug product is ready to be used when a specified amount of time has passed on the at least one timer.

[0011] In some embodiments, the specified amount of time is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

[0012] In some embodiments, the specified amount of time is selected to correspond to the amount of time that the active pharmaceutical ingredient (API) contained within the drug product will reach a desired temperature when placed in an environment within a standard room temperature range.

[0013] In some embodiments, the breakthrough temperature corresponds to a temperature outside the standard refrigeration temperature range.

[0014] In some embodiments, a drug product is provided that includes: a container configured to contain an active pharmaceutical ingredient (API); and a detector disposed adjacent to the container.

[0015] In some embodiments, the container comprises a syringe configured to contain the active pharmaceutical ingredient (API).

[0016] In some embodiments, the injector comprises an autoinjector.

[0017] In some embodiments, the temperature sensor determines the temperature of the active pharmaceutical ingredient (API) based at least in part on the temperature of the container.

[0018] In some embodiments, the detector is removably attached to the container.

[0019] In some embodiments, the detector includes a user-controlled activator configured to activate the temperature sensor.

[0020] In some embodiments, the at least one timer is configured to begin measuring a second lapse of time if the temperature of the drug product detected by the temperature sensor reaches or exceeds a second breakthrough temperature.

[0021] In some embodiments, the second breakthrough temperature is greater than the breakthrough temperature.

[0022] In some embodiments, a first timer of the at least one timer is configured to measure the time lapse if the breakthrough temperature is detected, and a second timer of the at least one timer is configured to measure the second time lapse if the second breakthrough temperature is detected.

[0023] In some embodiments, the lapse of time measured by the at least one timer is of a longer duration than the second lapse of time measured by the at least one timer.

[0024] In some embodiments, the at least one indicator is configured to generate the indication that the drug product is ready to be used if a second specified amount of time has elapsed on the at least one timer.

[0025] In some embodiments, the at least one indicator includes at least one of an audio indicator and / or a visual indicator.

[0026] In some embodiments, the visual indicator includes a first illuminator configured to be activated when the pharmaceutical product is ready to be used.

[0027] In some embodiments, the visual indicator includes a second illuminator configured to be activated if the drug product is not ready for use.

[0028] In some embodiments, the audio indicator is configured to produce a sound if the pharmaceutical product is ready to be used.

[0029] In some embodiments, the indicator comprises a graphical user interface (GUI) on a mobile device configured to indicate when the drug product is ready to be used.

[0030] In some embodiments, the mobile device is communicatively coupled to one or more of the temperature sensor and the timer.

[0031] In some embodiments, the graphical user interface (GUI) is configured to display an expected duration for an injection based at least in part on the detected temperature and the drug product.

[0032] In some embodiments, the detector includes a fluid configured to travel through the temperature sensor and the at least one timer.

[0033] In some embodiments, the detector includes a user-controlled activator configured to cause the fluid to travel from a reservoir associated with the user-controlled activator and to the temperature sensor when the user-controlled activator is activated.

[0034] In some embodiments, the temperature sensor includes a window configured to indicate that the detector is active.

[0035] In some embodiments, the fluid is configured to travel from the temperature sensor and through the at least one timer if the drug product reaches or exceeds the breakthrough temperature.

[0036] In some embodiments, the fluid is configured to travel through the at least one timer and to the at least one indicator within the specified amount of time.

[0037] In some embodiments, the specified amount of time corresponds to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

[0038] In some embodiments, the fluid is configured to travel from the temperature sensor and through a second timer of the at least one timer if the drug product reaches or exceeds a second breakthrough temperature.

[0039] In some embodiments, the fluid is configured to travel through the second timer and to the at least one indicator within a second specified amount of time.

[0040] In some embodiments, the second breakthrough temperature is greater than the breakthrough temperature, and wherein the second specified amount of time is greater than the specified amount of time.

[0041] In some embodiments, a method of indicating that a drug product is ready to be used is provided, the method comprising: detecting a temperature of the drug product with a temperature sensor; measuring a passage of time with at least one timer when the temperature of the drug product detected by the temperature sensor reaches or exceeds a breakthrough temperature; and generating an indication that the drug product is ready to be used with at least one indicator and when a specified amount of time has passed on the at least one timer.

[0042] In some embodiments, the specified amount of time is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

[0043] In some embodiments, the specified amount of time is selected to correspond to the amount of time that the active pharmaceutical ingredient (API) contained within the drug product will reach a desired temperature when placed in an environment within a standard room temperature range.

[0044] In some embodiments, the breakthrough temperature corresponds to a temperature outside the standard refrigeration temperature range.

[0045] In some embodiments, the method includes activating the temperature sensor with a user-controlled activator.

[0046] In some embodiments, the method includes measuring a second lapse of time with the at least one timer if the temperature of the drug product detected by the temperature sensor reaches or exceeds a second breakthrough temperature.

[0047] In some embodiments, the second breakthrough temperature is greater than the breakthrough temperature.

[0048] In some embodiments, a first timer of the at least one timer is configured to measure the time lapse if the breakthrough temperature is detected, and a second timer of the at least one timer is configured to measure the second time lapse if the second breakthrough temperature is detected.

[0049] In some embodiments, the lapse of time measured by the at least one timer is of a longer duration than the second lapse of time measured by the at least one timer.

[0050] In some embodiments, the method includes generating the indication that the drug product is ready to be used with the at least one indicator and when a second specified amount of time has elapsed on the at least one timer.

[0051] In some embodiments, the at least one indicator includes at least one of an audio indicator and / or a visual indicator.

[0052] In some embodiments, the method includes activating the at least one visual indicator if the drug product is ready to be used.

[0053] In some embodiments, the method includes activating a second visual indicator of the at least one visual indicator if the drug product is not ready to be used.

[0054] In some embodiments, the method includes activating the audio indicator to produce a sound if the pharmaceutical product is ready to be used.

[0055] In some embodiments, the method includes indicating on a graphical user interface (GUI) on the mobile device that the drug product is ready for use.

[0056] In some embodiments, the mobile device is communicatively coupled to one or more of the temperature sensor and the timer.

[0057] In some embodiments, the method includes displaying on the graphical user interface (GUI) an expected duration for an injection based at least in part on the detected temperature and the drug product.

[0058] In some embodiments, the method includes a fluid configured to travel through the temperature sensor and the at least one timer.

[0059] In some embodiments, the method includes using a user-controlled activator to cause the fluid to travel from a reservoir associated with the user-controlled activator and to the temperature sensor.

[0060] In some embodiments, in the event that the drug product reaches or exceeds the breakthrough temperature, the fluid travels from the temperature sensor and through the at least one timer.

[0061] In some embodiments, the fluid travels through the at least one timer and reaches the at least one indicator within the specified amount of time.

[0062] In some embodiments, the specified amount of time corresponds to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

[0063] In some embodiments, if the drug product reaches or exceeds a second breakthrough temperature, the fluid travels from the temperature sensor and through a second timer of the at least one timer.

[0064] In some embodiments, the fluid travels through the second timer and reaches the at least one indicator within a second specified amount of time.

[0065] In some embodiments, the second breakthrough temperature is greater than the breakthrough temperature, and wherein the second specified amount of time is greater than the specified amount of time.

[0066] In some embodiments, a detector is provided that is configured to be attached to a drug product containing an active pharmaceutical ingredient (API) therein, the detector comprising: a temperature sensor configured to detect a temperature of the drug product; at least one processor configured to calculate a change over time between the detected temperatures; and at least one indicator configured to generate an indication that the drug product is ready to be used when the calculated change over time between the detected temperatures meets or falls below a predefined threshold.

[0067] In some embodiments, the predefined threshold is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready to be used.

[0068] In some embodiments, calculating the change between the detected temperatures over time includes determining a difference between a first temperature and a second temperature, the first temperature and the second temperature being detected a predefined amount of time apart.

[0069] In some embodiments, the at least one processor is configured to generate a ratio of the difference between the first temperature and the second temperature to the predefined amount of time interval, and compare the ratio to the predefined threshold.

[0070] In some embodiments, a method for indicating that a drug product is ready to be used is provided, the method comprising: detecting the temperature of the drug product with a temperature sensor; calculating the change between the detected temperatures over time with at least one processor; and generating an indication that the drug product is ready to be used with at least one indicator and when the change in the calculated change between the detected temperatures over time meets or is below a predefined threshold.

[0071] In some embodiments, the predefined threshold is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready to be used.

[0072] In some embodiments, calculating the change between the detected temperatures over time includes determining a difference between a first temperature and a second temperature, the first temperature and the second temperature being detected a predefined amount of time apart.

[0073] In some embodiments, the at least one processor generates a ratio of the difference between the first temperature and the second temperature to the predefined amount of time interval and compares the ratio to the predefined threshold.

[0074] In some embodiments, a liquid crystal sensor is provided that is configured to be attached to a drug product that contains an active pharmaceutical ingredient (API) therein, the liquid crystal sensor comprising: a liquid crystal configured to change color as the drug product heats up to indicate an increased temperature of the drug product; and at least one indicator configured to indicate when the API within the drug product reaches a specified temperature or temperature range, wherein the specified temperature or temperature range indicates when the drug product is ready to be used.

[0075] In some embodiments, a portion of the liquid crystal is adjacent to the at least one indicator on the liquid crystal sensor and is configured to change color when the drug product is ready to be used.

[0076] In some embodiments, the liquid crystal includes a visual instrument that indicates the increasing temperature of the drug product as the drug product increases in temperature.

[0077] In some embodiments, the at least one indicator corresponds to an end of the visual instrument.

[0078] In some embodiments, the at least one indicator is configured to indicate an expected duration for the injection.

[0079] In some embodiments, any one or more of the features, characteristics, or elements discussed above with respect to any of the embodiments may be incorporated into any of the other embodiments mentioned above or described elsewhere herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Figure 1 A pharmaceutical product is shown having a detector disposed thereon for detecting the temperature of the pharmaceutical product and indicating when the pharmaceutical product is ready to be used, according to some embodiments.

[0081] Figure 2A A system diagram of a detector for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown according to some embodiments.

[0082] Figure 2B to Figure 2C An example detector for indicating when a pharmaceutical product is ready to be used is shown in accordance with some embodiments.

[0083] Figure 2D An example graphical user interface (GUI) for a personal computing device for indicating when a pharmaceutical product is ready to be used is shown in accordance with some embodiments.

[0084] Figure 2E An example printed circuit board (PCB) is shown of a detector for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used, according to some embodiments.

[0085] Figure 2F A schematic diagram of a detector for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown according to some embodiments.

[0086] Figure 3 A time graph is shown of the temperature rise of the outer surface of a drug product housing and a liquid contained within the housing to room temperature (eg, 21.7° C.) according to some embodiments.

[0087] FIG. 4A to FIG. 4E A detector for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown including a fluid and one or more substrates according to some embodiments.

[0088] FIG. 5A to FIG. 5H A liquid crystal sensor for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown in accordance with some embodiments.

[0089] Figure 6 A method for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown according to some embodiments. DETAILED DESCRIPTION

[0090] Described herein is a detector configured to be attached to a drug product to detect the temperature of the drug product and indicate whether the drug product is ready to be used based on a specified amount of time that has passed. The disclosed detector can detect when the drug product reaches a breakthrough temperature, and once the breakthrough temperature is reached or exceeded, it indicates whether the drug product is ready to be used based on a specified amount of time that has passed. The breakthrough temperature can be defined as a temperature outside the standard refrigeration range (e.g., 2°C to 8°C). In some embodiments, the breakthrough temperature can be between 10°C and 15°C (e.g., 12°C). Based on the drug product reaching one or more breakthrough temperatures, the detector can start a timer that is configured to measure the passage of time and indicate that the drug product is ready to be used after a specified amount of time has passed.

[0091] Traditionally, a user may refer to the instructions for use (IFU) that comes with a drug product (e.g., on a product label and / or package insert) to determine how and when to use the drug product. Additionally, a medical professional may verbally inform the user of the instructions for use of the drug product during a medical visit and / or in a written medical record. The instructions may include the waiting time required before using the drug product. The waiting time may be defined as the duration that a drug product stored in a controlled cooling environment (e.g., a refrigerator, a freezer, etc.) needs to stand in an ambient environment (e.g., standard room temperature, about 20°C to 22°C) before use. The waiting time may be required to allow the API of the drug product to warm up to the ambient temperature, thereby reducing the viscosity of the API to prepare for the correct injection of the API. The instructions may also include a maximum duration that the drug product cannot exceed when standing in an ambient environment. The API may expire after a predefined duration (e.g., between 4 hours and 8 hours) outside a controlled cooling environment, making it unsafe to use the API.

[0092] During the use of the drug product, these instructions are often forgotten, misplaced, confused (e.g., with another drug product) or ignored (e.g., when the user is in a hurry). The user may attempt to use the drug product directly after taking it out of the cooling environment, and in the case of the drug product being a drug product that requires injection, failure to comply with the waiting time may result in extended injection time, inability to inject the product and / or pain at least at the injection site. Each of these problems may be at least due to low temperatures and the high viscosity of the API produced therefrom. The injection time may be defined as the duration required to fully inject the drug product into the user's body. In some cases, the user may forget to track the time after taking out the drug product from the controlled cooling environment, and the duration of leaving the product in the surrounding environment exceeds the maximum duration that the product can stay outside the cooling environment. In this case, the drug product may lose its efficacy and / or expire, making it inappropriate and unsafe to use the product.

[0093] In some cases, despite the user complying with the recommended waiting time provided in the IFU and / or informed by the medical professional, the drug product may require more or less time to reach the appropriate use temperature. This time variation to reach the appropriate use temperature may be due at least in part to the variable room temperature that the product needs to stand before use. In some cases, the drug product may never reach the appropriate use temperature. Currently, there is no way for the user to know that the drug product is ready for use in advance of the indicated waiting time, or that additional standing time is required before use. The detector described herein detects the temperature of the drug product and activates one or more timers based on detecting at least one breakthrough temperature. The timer can be configured using various algorithms to indicate when the drug product is ready to be used based on the time in the past and / or the temperature reached. The detector provided can more efficiently and effectively inform the user when the drug product is ready to be used, mitigate any risk of user confusion, and improve the user's compliance with the waiting time associated with the active pharmaceutical ingredient (API).

[0094] The detector described herein may include a temperature sensor, at least one timer, and at least one indicator. In some embodiments, the temperature sensor may detect the temperature of the drug product, and the first timer may start measuring the time lapse when the temperature sensor detects that the drug product has reached or exceeded the breakthrough temperature. In some embodiments, the second detector may be configured to measure the second time lapse when the temperature sensor detects that the drug product has reached the second breakthrough temperature. At least one indicator may generate an indication that the drug product is ready to be used when the prescribed amount of time measured by the first timer or the second timer has passed. In some embodiments, the detector may require user activation to start detecting the temperature of the drug product. In some embodiments, the indicator may include one or more illuminators, which are configured to illuminate when the drug product is not ready to be used and when the drug product is ready to be used. In some embodiments, the sensor may be coupled to a personal computing device (e.g., a desktop computer, a tablet computer, a mobile device, a smart watch, etc.) to indicate to the user when the drug product is ready to be used / not ready to be used.

[0095] In some embodiments, the detector may include a fluid that travels through one or more fluid pathways (e.g., a timer) if the temperature of the fluid reaches or exceeds one or more breakthrough temperatures. The fluid may travel through the one or more fluid pathways to an indicator within a specified amount of time to indicate that the drug product is ready to be used. In some embodiments, the detector may require user activation to cause the fluid to travel to the temperature sensor.

[0096] In some embodiments, the detector may be embodied in a liquid crystal sensor including liquid crystals that may be configured to change color based on the elevated temperature of the drug product and indicate whether the drug product is ready to be used after a certain time has elapsed.

[0097] The detectors described herein may be associated with a variety of pharmaceutical products. For example, pharmaceutical products may include drug delivery devices (e.g., auto-injectors, syringes, etc.), nasal sprays, atomizers, eye droppers, or containers (e.g., vials, bottles, cartridges, etc.) containing or configured to contain active pharmaceutical ingredients (APIs) (e.g., drugs, medicaments, antibiotics, vaccines, drugs, etc.). Injection devices may include syringes (e.g., hypodermic syringes, oral delivery syringes, prefilled syringes, glass syringes, plastic syringes, etc.), on-body delivery systems (OBDS), patch pumps, automatic syringe systems (e.g., pumps, patch pumps, and pens), manual syringe systems, injection pumps, etc.

[0098] In some embodiments, a drug product may be provided with a detector attached to the product. In some embodiments, a user may need to attach a detector to the product before using the drug product. In some embodiments, the detector and drug product may be single-use and disposable. In some embodiments, the detector may be reusable. In some embodiments, a drug product may include an API contained in a container (e.g., a vial, a bottle, a cartridge, etc.), and when a detector associated with the container indicates that the drug product is ready to be used, the user can remove the API from the container with an injection device.

[0099] In some embodiments, the active pharmaceutical ingredient (API) may need to be stored in a cool environment (e.g., refrigerator, freezer, etc.) until use. Example APIs may include eye / ear drops, reconstituted antibiotics, injections, and other macromolecular drugs in liquid form (e.g., Nipocalimab).

[0100] The API list provided above is not intended to be exhaustive and may be extended to any drug, medicine, medicament, antibiotic, vaccine, etc. not expressly stated herein. One of ordinary skill in the art will be able to reasonably apply the detector disclosed herein to a variety of pharmaceutical products, including various containers, syringes, etc., and the API contained therein.

[0101] Referring now to the drawings, like parts are designated throughout the specification and drawings by like reference numerals, respectively.

[0102] Pharmaceutical products for use with the detector

[0103] The detectors disclosed herein may be configured to be attached to a variety of pharmaceutical products containing active pharmaceutical ingredients (APIs).

[0104] Figure 1 An example drug product with a detector 100 attached thereto is shown. The drug product 102 may include, for example, a drug delivery device, a nasal spray, a sprayer, an eye dropper, a container, or another reservoir for containing an API. As mentioned above, the example drug delivery device may include an injection device, such as a syringe (e.g., a hypodermic syringe, an oral delivery syringe, a prefilled syringe, a glass syringe, a plastic syringe, etc.), an on-body delivery system (OBDS), a patch pump, an automatic syringe system (e.g., a pump, a patch pump, and a pen), a manual syringe system, a syringe pump, etc. In some embodiments, an example container may include a vial, a bottle, a cartridge, etc. The containing portion of the drug product described above (e.g., a drug delivery device, a container, etc.) may be referred to as a "container" hereinafter.

[0105] In some embodiments, the detector 100 may be configured within the packaging of the drug product 102. In some embodiments, the detector 100 may be configured on an exterior portion of the packaging of the drug product 102. In some embodiments, at least a portion of the detector 100 may be configured within a reservoir of the drug product 102 such that the detector 100 may physically contact the API contained within the drug product. In each embodiment in which at least a portion of the detector 100 (e.g., a temperature sensor) is not in contact with the API of the drug product, one or more algorithms may be configured to infer the temperature of the API based on the temperature of the container, packaging, etc.

[0106] For example, the detector 100 may be configured to detect the temperature of the outer surface of the drug product 102 to determine the temperature of the API contained within the container, such as by measuring at least Figure 3 Described in more detail. In some embodiments, the detector 100 may be attached to the packaging of the drug product or the outer surface of the drug product, and may be configured to detect the temperature of the environment (e.g., air) directly surrounding the drug product to determine the temperature of the API. In some embodiments, the detector 100 may be configured to be attached to containers containing one or more materials (such as glass and polymers (e.g., polyvinyl chloride, polystyrene, polypropylene, polyethylene, polyester, nylon, polyvinylidene chloride, polycarbonate, etc.)) and detect the temperature of these containers. Many of these materials can be insulators; therefore, via experiments and / or algorithms, the temperature of the API within the container can be determined by considering the properties of heat transfer between the container, the environment, and the API, as will be described in more detail below.

[0107] One or more of the containers of the detector 100 and the drug product 102 may include an adhesive material so that the detector 100 may be adhered to the drug product, for example, by the user and / or before the drug product 102 is provided to the user. In some embodiments, the drug product 102 and the detector 100 may be manufactured and / or provided as a single unit so that the detector 100 is not configured to be removable from the drug product 102. In some embodiments, the detector 100 may be provided on a removable sleeve that is configured to be attached around at least a portion of the drug product 102. In some embodiments, as mentioned above, the drug product 102 may be single-use and disposable. Similarly, the detector 100 may be single-use and disposable. In some embodiments, each of the detector 100 and / or the drug product 102 may be reusable and / or semi-reusable. For example, a user may adhere a single reusable detector 100 to different single-use drug products 102 every day (or every few hours, days, months, etc.).

[0108] The detector 100 may be embodied in an electrical system, a fluid-based system, or a liquid crystal sensor system, as will be described below. FIG. 2A to FIG. 2F , FIG. 4A to FIG. 4E as well as FIG. 5A to FIG. 5H Each of these systems is described in more detail.

[0109] Electrical Detectors for Pharmaceutical Products

[0110] In some embodiments, the above Figure 1 The described detector 100 may be embodied in an electrical detection system that includes one or more electrical components (e.g., one or more processors, temperature sensors, illuminators, etc.) that are communicatively coupled (e.g., via wired and / or wireless communications) to detect the temperature of a drug product, measure the passage of time when one or more breakthrough temperatures are reached or exceeded, and indicate when the drug product is ready for use based on the passage of time. FIG. 2A to FIG. 2F Features of an electrical detector configured to detect the temperature of a pharmaceutical product and indicate whether the pharmaceutical product is ready for use based on a specified lapse of time are shown in accordance with some embodiments.

[0111] Figure 2A A system diagram of a detector 200 configured to detect the temperature of a pharmaceutical product and indicate when the pharmaceutical product is ready to be used is shown. The detector 200 may include the Figure 1Any one or more features of the detector 100 described. The detector 200 may include a user-controlled activator 204, a temperature sensor 206, an illuminator (e.g., a light indicator) 208, a speaker 210, a processor 212, a memory 214, and a power source (e.g., a battery) 216. Each of the illustrated components of the detector 200 may be embodied by more than one component; for example, the detector 200 may include multiple processors 212, temperature sensors 206, illuminators 208, etc. In some embodiments, each of the components of the detector 200 may be communicatively coupled to each other, such that each component may send signals to and / or receive signals from other components of the detector 200. In some embodiments, each of these components may be communicatively coupled to at least one or more processors 212, such that the processor 212 is configured to receive signals from each of the components of the detector 200 and send one or more signals to the components of the detector 200 to perform actions based on the received signals.

[0112] In some embodiments, based on the received signal, the processor 212 may be configured to activate and / or deactivate one or more components illustrated in the detector 200 (e.g., the temperature sensor 206, the illuminator 208, and / or the speaker 210). In some embodiments, the processor 212 may include at least one timer configured to measure the passage of time (e.g., once the breakthrough temperature is detected by the temperature sensor 206). In some embodiments, the timer may measure the time starting at zero and counting up to a predefined time. In some embodiments, the timer may measure the time starting at a predefined time and counting down to zero. In some embodiments, the timer is a separate component that is communicatively coupled to at least the processor 212 and / or one or more components of the detector 200 (e.g., the temperature sensor 206). In some embodiments, the processor 212 may include multiple timers configured to measure different passages of time to indicate when the drug product is ready to be used after a specified amount of time has passed. In some embodiments, the processor 212 may include one or more memories, such as a memory 214 (e.g., the memory 214 may be within the processor 212).

[0113] like Figure 2A As shown, the detector 200 may include a user-controlled activator 204. The user-controlled activator 204 may include one or more touch-sensitive buttons, switches, capacitive touch sensors, pressure sensors, etc. configured to receive user input indicating a request to activate (e.g., turn on) the detector 200. For example, Figure 2BThe detector 200 including a user-controlled activator 204 is illustrated, wherein the activator can be a touch-sensitive button. In some embodiments, the user-controlled activator 204 can be configured to send a signal to one or more components of the detector 200 (e.g., temperature sensor 206, illuminator 208, and / or speaker 210) upon receiving user input (e.g., directly and / or indirectly via processor 212). For example, the user-controlled activator 204 can be configured to receive user input and send a signal to the temperature sensor 206 so that the temperature sensor 206 activates and begins detecting the temperature of the drug product. In some embodiments, the user-controlled activator 204 can instead or additionally send a signal to the processor 212 so that the processor can send a signal to the temperature sensor 206 to activate the sensor. The user can engage (e.g., tap, push, etc.) the user-controlled activator 204 within a specified amount of time (e.g., 1 second, 2 seconds, 3 seconds) to activate the detector 200. In some embodiments, in response to a user activating the detector 200 via the user-controlled activator 204, a light indicator (e.g., Figure 2B The illuminator 220 in the detector 200 may be configured to illuminate (e.g., based on a signal received from the user-controlled activator 204 and / or the processor 212). The illuminator may communicate, for example, that the detector 200 is active (e.g., detecting at least the temperature of the drug product), but is not yet ready to be used.

[0114] In some embodiments, the detector 200 may include one or more temperature sensors 206. The temperature sensors 206 may be configured to continuously detect the temperature of the drug product (e.g., Figure 1In some embodiments, the temperature sensor 206 may be disposed within the detector 200 so that at least a portion of the temperature sensor 206 is adjacent to and / or in contact with the outer surface of the drug product. As described above, in some embodiments, the temperature sensor 206 may be disposed on the packaging of the drug product and / or configured to measure the temperature of the packaging of the drug product. In some embodiments, the temperature sensor 206 may be disposed within the drug product to directly detect the temperature of the API. In some embodiments, the temperature sensor 206 may be configured to detect the temperature of the environment (e.g., air) directly surrounding the drug product. The temperature sensor 206 may include one or more thermocouples, resistance temperature detectors (RTDs), thermistors (e.g., negative temperature coefficient (NTC) thermistors), and / or semiconductor-based integrated circuits (ICs). For example, the temperature sensor 206 may include an NTC thermistor so that when the temperature rises, the resistance of the thermistor decreases. In some embodiments, the thermistor may include a polymer or ceramic material. The temperature sensor 206 may be communicatively coupled to one or more components of the detector 200. For example, the temperature sensor 206 may be configured to receive input (e.g., a signal) from the user-controlled activator 204 (e.g., directly and / or indirectly via the processor 212). For example, as described above, the user-controlled activator 204 may send a signal to the temperature sensor 206, and the temperature sensor 206 may be activated based on the received signal.

[0115] In some embodiments, the temperature sensor 206 can be configured to send / receive signals to / from the processor 212. For example, the temperature sensor 206 can continuously detect the temperature of the drug product as the drug product warms up to an appropriate use temperature (e.g., toward ambient temperature). For each detected temperature, the temperature sensor 206 can send a signal indicating the detected temperature to the processor 212. The processor 212 can determine when the drug product is ready to be used based on the detected temperature and / or the passage of time, as will be described in more detail below.

[0116] In some embodiments, upon detecting a breakthrough temperature of the drug product, the temperature sensor 206 may be configured to cause activation of one or more timers (e.g., directly and / or indirectly via the processor 212). As defined above, the breakthrough temperature of the drug product may be a temperature outside the standard refrigeration range (e.g., 2°C to 8°C). In some embodiments, the breakthrough temperature may be between 10°C and 15°C (e.g., 12°C) so that a small fluctuation in temperature above the standard refrigeration range for a short period of time may not be classified as a breakthrough temperature. In some embodiments, the initial temperature detected by the temperature sensor 206 may be the breakthrough temperature. In some embodiments, a value for the breakthrough temperature may be stored in a temperature library of the memory 214 so that the processor 212 may retrieve temperature data from the memory 214 to classify the signal as corresponding to the detected breakthrough temperature.

[0117] In some embodiments, the timer can measure the time lapse after the breakthrough temperature is detected for a specified amount of time. The specified amount of time can be based on one or more factors, such as the material of the container of the drug product, the detected ambient room temperature and / or the API contained in the container. For example, the memory 214 can be configured to store a library of specific times associated with different drug product containers, APIs and room temperatures. The system can be configured to determine the room temperature to select the specified amount of time, for example, using at least the detected temperature of the container, as will be described in more detail below. In some embodiments, as mentioned above, the timer of the processor 214 can be configured to count from zero until the specified time. In some embodiments, the timer can be configured to count down from the specified time to zero.

[0118] In some embodiments, the temperature sensor 206 may continue to detect the temperature of the drug product after detecting the breakthrough temperature. In some embodiments, the temperature sensor 206 may detect a second breakthrough temperature greater than the first breakthrough temperature. Based on the second breakthrough temperature, the temperature sensor 206 (e.g., directly or indirectly via the processor 212) may be configured to cause the timer to measure a second time lapse. In some embodiments, the second time lapse may be less than the first time lapse. In some embodiments, the detector 200 may include more than one timer (e.g., 2, 3, 4, 5 or more timers) configured to measure each time lapse of interest (e.g., optionally embodied in the processor 212). In some embodiments, the processor 212 may be configured to modify the specified amount of time that the timer is counting, rather than measuring the second time lapse based on the second detected breakthrough temperature. For example, in the case where the timer is counting from zero, the processor 212 may reduce the time that the timer is counting. In some embodiments, in the case where the timer starts counting time from a predefined value associated with the first breakthrough temperature and / or the drug product based on the second detected breakthrough temperature, the processor 212 may reduce the current time of the timer.

[0119] For example, the detector 200 may be configured to indicate that the drug product is not ready to be used when the detected temperature is less than the breakthrough temperature (e.g., 15° C. in this example). When the temperature sensor 206 detects a temperature greater than or equal to 15° C., the processor 212 may be configured to start measuring a first time lapse. For example, the timer may measure a time lapse of 30 minutes so that the drug product will be ready to be used after 30 minutes have passed. In some embodiments, the temperature sensor 206 may continue to detect the temperature of the drug product after the first timer has begun measuring the time lapse. When the temperature sensor 206 detects a second breakthrough temperature (e.g., 18° C. in this example), the processor 212 may be configured to start measuring a second time lapse. For example, based on the second breakthrough temperature, the timer may be configured to measure a time lapse of 5 minutes. The detector 200 may be configured so that the user is notified that the drug product is ready to be used when the first time lapse or the second time lapse (e.g., whichever occurs first) has passed.

[0120] In some embodiments, the detector 200 may include a third timer configured to measure the passage of time regardless of the detected breakthrough temperature. For example, the third timer may be configured to measure the passage of time once the detector 200 is activated, and after a predefined amount of time has passed, may indicate that the drug product is ready to be used.

[0121] In some embodiments, in addition to or in lieu of measuring the passage of time after the breakthrough temperature has been reached and / or exceeded, the processor 212 may also be configured to determine the relationship between the passage of time and the detected temperature to determine whether the drug product is ready to be used. For example, the processor 212 may determine when the drug product is ready to be used by continuously tracking the temperature of the drug product over time. The processor 212 may analyze the ratio of the temperature change over time, and in the case where the processor 212 detects a low, stable ratio (e.g., less than 1), the processor 212 may cause one or more indicators (described in more detail below) to indicate that the drug product is ready to be used. For example, the processor 212 may continuously compare two temperatures detected at a predefined duration time interval (e.g., 1 minute) to determine a ratio (e.g., second temperature-first temperature / 1 minute). In some embodiments, the processor 212 may compare two temperatures detected at a smaller duration time interval (e.g., 15 seconds, 30 seconds, 45 seconds, etc.) or a larger duration time interval (e.g., 2 minutes, 3 minutes, 4 minutes, etc.). Based on the relationship between temperature and time, processor 212 may be able to determine that the drug product has equilibrated to an appropriate use temperature (eg, ambient temperature) and is ready to be used.

[0122] Figure 2F An example schematic diagram having one or more logic gates for determining when a drug product is ready to be used based at least on the algorithm described above is illustrated. For example, when a user engages a user-controlled activator (e.g., a switch) 204, a timer 224 may be configured to begin measuring the passage of time and a temperature sensor 206 (e.g., a negative temperature coefficient (NTC) thermistor) may simultaneously begin detecting the temperature of the drug product. The timer 224 (e.g., optionally embodied in the processor 212) and the temperature sensor 206 may send signals indicating the measured time and the detected temperature, respectively. Based on the received signals, the processor (e.g., a computer processing unit (CPU)) 212 may be configured to analyze changes in temperature. As Figure 2FAs shown, based on the analysis, the processor 212 may transmit a signal to one or more logic gates 226 that are communicatively coupled to one or more indicators. For example, when the temperature change is greater than 1, the processor 212 may send an "off" (e.g., binary 0) signal to a "NOT" logic gate 226 that is communicatively coupled to an illuminator (e.g., an LED light indicator) 220 (e.g., configured to perform an operation opposite to the received signal). As will be described in more detail below, the illuminator 220 may be configured to indicate to the user when the drug product is not ready to be used. The processor 212 may also (e.g., substantially simultaneously) send an "off" signal to an "AND" logic gate. The "AND" logic gate may receive input from an additional component of the detector 200 that is configured to determine when the detector 200 is stable. For example, when the detector 200 is activated with the user-controlled activator 204, the second timer may be configured to begin measuring a predefined time lapse (e.g., at least 1 minute). Once the time lapse has elapsed, the switch may be actuated so that a signal may be sent to the "AND" logic gate. Upon two matching signals (e.g., binary 1) from the components, an illuminator (e.g., LED light indicator) 208 communicatively coupled to the "AND" logic gate may be activated. In some embodiments, when the temperature change is less than 1, the processor 212 may send an "on" (e.g., binary 1) signal to the logic gate 226. The "NOT" logic gate may send a signal to the illuminator 220 to deactivate the illuminator. On the other hand, the "AND" logic gate may send a signal to one or more indicators (e.g., illuminator 208, speaker 210) to indicate that the drug product is ready to be used upon receiving two matching signals (e.g., binary 1).

[0123] In some embodiments, (e.g., once the drug product is removed from a refrigerator) the processor 212 may use an initial temperature of an environment outside of a controlled cooling environment to determine when the drug product is ready to be used. For example, the temperature sensor 206 may detect the temperature of the drug product during an initial stabilization period that occurs when the detector 200 is activated (e.g., via a user-controlled activator 204). The initial stabilization period may be a predefined duration (e.g., 1 minute, 90 seconds, 2 minutes, etc.). For example, the temperature sensor 206 may detect a first temperature at an activation time (time1=0) and a second temperature at a predefined time after the activation time, where the predefined time is based on a calculated time constant of the detector 200 (e.g., time2=0.7*time constant). The time constant of the detector 200 may be experimentally determined by measuring a change in the temperature of the drug product detected by the detector 200 and recording, for example, a point at which 63% settling has occurred. Using the first detected temperature and the second detected temperature, the processor 212 of the detector 200 may estimate an ambient temperature (e.g., room temperature). For example, the relationship between the estimated ambient temperature and the detected first and second temperatures may be embodied in the following formula:

[0124] T environment = T1 + 2 (T2 - T1)

[0125] Equation 1. Estimated ambient temperature

[0126] In some embodiments, the relationship between the first temperature and the second temperature used to determine the ambient room temperature may be different from the relationship provided above in Equation 1. In some embodiments, one or more of the estimated ambient temperature, the first temperature, and the second temperature may be stored, for example, in a memory (e.g., a temporary memory of the processor 212, the memory 214, etc.). Based on the estimated ambient temperature, the processor 212 may determine a target temperature (e.g., the temperature at which the drug product will be ready for use) and / or a maximum waiting time (e.g., the maximum time to wait before using the drug product). In some embodiments, the target temperature may be a fraction of the estimated ambient temperature (e.g., 90%, 95%, 98%, or another specified value). In some embodiments, the maximum waiting time may additionally or instead be based on the type of API in the container, the material of the container, the volume of the API, etc. For example, as described above, the processor 212 may access the memory 214 that stores the target temperature associated with the determined ambient temperature and the maximum waiting time associated with the determined waiting time and one or more of the one or more factors provided above.

[0127] In some embodiments, the processor 212 may begin measuring the passage of time (e.g., limited by a maximum wait time) when determining the estimated ambient temperature. In some embodiments, the maximum wait time may be independent of the estimated room temperature, such that the timer of the processor 212 begins measuring the passage of time (limited by a predetermined maximum wait time) when the detector 200 is activated. When determining the target temperature, the temperature sensor 206 may be configured to periodically detect the temperature of the drug product over time (e.g., at least every 5 seconds, 10 seconds, 20 seconds, 30 seconds, or 60 seconds). The processor 212 may be configured to receive a signal indicating the detected temperature from the temperature sensor 206, and the detected temperature may be compared to the target temperature. In some embodiments, the processor 212 may be configured to activate one or more indicators when a temperature equal to or greater than the target temperature is detected or when the maximum wait time is reached (whichever occurs first).

[0128] In some embodiments, the processor 212 may be configured to measure the time elapsed until a breakthrough temperature (e.g., 12° C., 15° C., or another predefined temperature) is detected when the detector 200 is activated (e.g., via a user-controlled activator 204). Based on the amount of time that elapses to reach the breakthrough temperature, the processor 212 may determine the amount of time required for the ambient temperature (e.g., room temperature) and / or the drug product to reach an appropriate use temperature. For example, as described above, the temperature sensor 206 may periodically detect the temperature of the drug product and compare the detected temperature to the determined appropriate use temperature to identify whether the drug product is ready to be used. In some embodiments, the temperature sensor 206 may activate one or more timers (e.g., embodied in the processor 212) and measure the time elapsed based on the determined amount of time required for the drug product to reach an appropriate use temperature.

[0129] In some embodiments, processor 212 may be configured to measure a specified amount of time when detector 200 is activated, regardless of the temperature of the environment outside of the controlled cooling environment.

[0130] In some embodiments, the processor 212 may apply one or more of the methods (e.g., algorithms) described above to determine when the drug product is ready to be used. For example, the processor 212 may use a combination of algorithms and provide an indication that the drug product is ready to be used when it is determined that the scenarios described above have occurred (e.g., whichever scenario occurs first may cause the indication).

[0131] In some embodiments, the detector 200 may include one or more indicators configured to indicate that the drug product is ready to be used. As mentioned above, the detector 200 may additionally include one or more indicators configured to indicate when the drug product is not ready to be used (e.g., Figure 2B to Figure 2C 220 as illustrated in ). In some embodiments, one or more indicators of the detector 200 may include an illuminator 208 and / or a speaker 210. In some embodiments, the illuminator 208 may include one or more light emitting diodes (LEDs). In some embodiments, the illuminator 208 may be configured to receive a signal sent from the processor 212 indicating that the drug product is ready to be used. For example, the processor 212 may be configured to send a signal to the illuminator 208 when the specified amount of time mentioned above has passed. In some embodiments, the processor 212 may be configured to send a signal to the illuminator 208 when it is determined that the appropriate use temperature has been reached (e.g., before the specified time has passed). In some embodiments, the processor 212 may cause an illuminator configured to indicate to a user that the drug product is not ready to be used (e.g., Figure 2B to Figure 2C 220 in the illuminator) is deactivated when a specified time has passed and / or when an appropriate use temperature is reached. In some embodiments, illuminator 220 may be configured to be deactivated substantially at the same time that illuminator 208 is activated.

[0132] In some embodiments, the illuminator 208 may be configured to illuminate for a predefined duration. For example, the illuminator 208 may illuminate for any duration (e.g., seconds, minutes, or hours) until a specified amount of time (e.g., 4 hours, 5 hours, 6 hours, 7 hours, or 8 hours). In some embodiments, the timer of the processor 212 may measure the amount of time that the drug product has been ready for use, and may indicate that the drug product should not be used after being ready for a predefined duration (e.g., 4 hours). For example, after the predefined duration, the illuminator 208 may be deactivated (e.g., neither the illuminator 208 nor the illuminator 220 are activated). In some embodiments, the detector 200 may include an additional indicator configured to illuminate after a predefined duration to indicate that the drug product is expired (e.g., Figure 2C 221 in the control panel). For example, various APIs may be unsafe to use after being left outside of a controlled cooling environment for a predefined duration (e.g., 2, 4, 6, 8 hours). Illuminator 221 may be configured to illuminate once a predefined duration has elapsed, which duration corresponds to the API of the drug product. By deactivating illuminator 208 and / or activating illuminator 221 after the predefined duration, detector 200 may indicate a time window for safe use of the drug product.

[0133] In some embodiments, the illuminator 208 may be communicatively coupled to the user-controlled activator 204 (e.g., directly or indirectly via the processor 212) such that a user may engage the user-controlled activator 204 to deactivate the illuminator 208. In some embodiments, a user may engage the user-controlled activator 204 to pause and / or power down the detector 200. In some embodiments, the detector 200 may include one or more sensors (not illustrated) configured to detect when a drug product has been used and / or is currently being used, and the illuminator 208 may be configured to deactivate upon determining that the drug product has been used.

[0134] In some embodiments, the illuminator 208 (and / or Figure 2B to Figure 2C 220) can be configured to illuminate and / or flash continuously. For example, as the drug product approaches a ready-to-use state, the illuminator can flash according to a predefined pattern corresponding to the passage of time. For example, the illuminator 220 can initially flash at a slower rate, and as the drug product reaches a time and / or temperature suitable for use, the rate at which the illuminator flashes can increase. In some embodiments, the illuminator 220 can initially flash at a faster rate, and can reduce the rate as the drug product approaches a ready-to-use state (e.g., based on a measured temperature and / or passage of time).

[0135] In some embodiments, the detector 200 may include an array of illuminators (e.g., Figure 2C), the array of illuminators is configured to indicate the status of the drug product as the drug product reaches an appropriate use temperature and / or time of use. For example, the detector 200 may include at least 2, 3, 4, 5, 6, 7, or 8 illuminators configured to indicate the status of the drug product (e.g., not ready, ready, and / or expired). In some embodiments, the array of illuminators 220 may be configured to illuminate gradually as time passes and / or the temperature of the drug product approaches an appropriate use temperature. For example, a first illuminator may be activated when the detector 200 is activated, a second illuminator may be activated a specified amount of time after activation of the detector and the first illuminator, a third illuminator may be activated a specified amount of time after activation of the second illuminator, and so on, until the illuminator 208 corresponding to when the device is ready to be used is activated. In some embodiments, multiple illuminators 220 may be configured to illuminate gradually as a breakthrough temperature is detected. For example, upon detection of a first breakthrough temperature, a first illuminator may be activated; upon detection of a second breakthrough temperature, a second illuminator may be activated; upon detection of a third breakthrough temperature, a third illuminator may be activated, and so on, until an appropriate use temperature is reached and / or a prescribed time has elapsed. In some embodiments, the illuminators may include one or more colors (e.g., red, blue, green, white, yellow, etc.). For example, illuminator 208 may illuminate a first color (e.g., green), and illuminator 220 may illuminate a second color (e.g., red) that is different from the first color.

[0136] like Figure 2B to Figure 2C As shown, each of the illuminators 208, 220, and 221 may correspond to a text label and / or icon on the detector 200 to indicate that the drug product is ready / not ready to be used. For example, the detector 200 may include a label (e.g., "Not Ready to Use," "Not Ready," "Active," "On," etc.) adjacent to the illuminator 220, which is configured to indicate that the detector 200 is active but the drug product is not yet ready to be used. Similarly, the detector 200 may additionally include a label (e.g., "Ready to Use," "Ready," etc.) adjacent to the illuminator 208, which is configured to indicate that the drug product is ready to be used. The detector 200 may additionally include a label (e.g., "Expired," "Expired," etc.) adjacent to the illuminator 221, which is configured to indicate that the drug product has expired, for example, due to the amount of time outside the controlled cooling environment reaching or exceeding the maximum amount of time allocated.

[0137] In some embodiments, in addition to or in lieu of activating the illuminator 208, the processor 212 may also send a signal to the speaker 210, which is configured to indicate that the drug product is ready to be used. In some embodiments, the speaker 210 may include a multi-tone and / or piezoelectric sounder (e.g., a buzzer). The speaker 210 may generate an audible sound (e.g., a tone, an alarm, a noise, etc.) in response to receiving a signal from the processor 212. In some embodiments, the speaker 210 may generate a continuous or discontinuous (e.g., a beep pattern) sound. In some embodiments, the speaker 210 may be configured to generate a sound that lasts for a predefined duration. For example, the speaker 210 may generate a sound that lasts less than or equal to 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, or 30 seconds. In some embodiments, the speaker 210 may generate a noise that lasts greater than or equal to 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, or 30 seconds. In some embodiments, the speaker 210 may be communicatively coupled to the user-controlled activator 204 (e.g., directly or indirectly via the processor 212) so that the user can engage the user-controlled activator 204 to deactivate the speaker 210. In some embodiments, the detector 200 may include one or more sensors (not illustrated) configured to determine when the drug product has been used and / or is currently being used, and based on determining that the drug product is being used, the speaker 210 may be configured to be deactivated. In some embodiments, the detector 200 may include one or more volume controls (not illustrated) so that the user can control the volume of the sound produced by the speaker 210.

[0138] like Figure 2A As shown, the detector 200 may be communicatively coupled to a personal computing device 218 for indicating when a drug product is ready to be used via wireless communication (e.g., WiFi, Bluetooth, Zigbee, etc.). The personal computing device 218 may include a mobile device, a tablet computer, a desktop computer, a smart watch, etc. In some embodiments, the detector 200 may include one or more processors configured to send and / or receive signals from the personal computing device 218 (i.e., different from the processor 212 that may be configured to send and / or receive signals from components within the detector 200). Figure 2DAn example mobile computing device 218 with a graphical user interface (GUI) 222 is illustrated. As shown, the GUI 222 of the mobile computing device 218 can be configured to indicate when the drug product is ready to be used. In some embodiments, the GUI 222 can be configured to indicate when the drug product is not ready to be used. The GUI 222 can provide a detected temperature (e.g., the temperature of the container) when the drug product is ready / not ready to be used. In some embodiments, the mobile computing device 218 can be configured to generate a notification when the drug product is ready to be used (e.g., based on the temperature of the drug product and / or the time elapsed). For example, the mobile computing device 218 can generate a notification (e.g., a sound, vibration, text notification, etc.) when the drug product is ready to be used, although the mobile computing device does not currently display the GUI 222. In some embodiments, the GUI 222 can additionally provide information related to the API to the user (e.g., the type and / or dosage of the API, the expiration date, etc.).

[0139] In some embodiments, GUI 222 may display the expected injection time. The injection time may be defined as the expected duration for injecting the API, for example, when the drug product includes an auto-injector. The injection time may be dynamically updated (e.g., reduced), for example, as the auto-injector injects the API into the user. In some embodiments, the processor 212 may include one or more sensors configured to detect when the auto-injector has started and / or completed the injection, and the data may be sent to the mobile computing device 218 for display on the GUI 222. In some embodiments, the auto-injector may experience a piston delay based on the detected temperature (e.g., the time difference between the end of the injection completion and the stopper stroke in the auto-injector detected by the detector 200), which may be considered when determining when the injection has been completed. In some embodiments, the injection data of a given patient may be tracked by GUI 222 and sent to, for example, an electronic health record (EHR) associated with the patient and accessible to a medical professional to allow the medical professional to view the patient's compliance with its dosing regimen.

[0140] In some embodiments, the detector 200 may additionally include a display (not illustrated) that is communicatively coupled to one or more components of the detector 200 (e.g., the processor 212) and is configured to provide at least a portion of the information described above with respect to the GUI 222 of the mobile computing device 218. For example, the detector 200 may include a liquid crystal display (LCD) that may display an expected injection time, a detected temperature of a drug product, a wait time, etc. In some embodiments, the detector 200 may include one or more illuminators (e.g., illuminators 208, 220, 221, etc.) in combination with the LCD display.

[0141] Figure 2E An example printed circuit board (PCB) implementation of detector 200 is shown. In some embodiments, user-controlled activator 204 may include a PCB switch. In some embodiments, processor 212 may include a microcontroller. In some embodiments, temperature sensor 206 may include a thermistor. The PCB of detector 200 may include multiple indicators. For example, detector 200 may include speaker 210 (e.g., piezoelectric sounder), illuminator 208 (e.g., LED) configured to indicate when the drug product is ready to be used, and illuminator 220 (e.g., LED) configured to indicate when the drug product is not ready to be used. In some embodiments, power supply 216 of detector 200 may include battery (e.g., single-use or rechargeable battery). In some embodiments, the battery may be configured to be removable from the holder of the PCB so that the battery may be removed after the use of detector 200 (e.g., when detector 200 and / or drug product is single-use). The PCB of detector 200 may be stored in a housing configured to be attached to the drug product. In some embodiments, the PCB of detector 200 is embodied in the housing of the drug product. Figure 1 Example housings for the detector 100 and the pharmaceutical product 102 are illustrated in FIG.

[0142] An example use of the electronic detector 200 is provided herein. In some embodiments, a user may remove a drug product with the detector 200 attached thereto from a controlled cooling environment (e.g., a refrigerator) and from the packaging of the drug product, and activate the detector 200 via a user-controlled activator 204, which may cause the temperature sensor 206 to begin automatically detecting the temperature of the drug product. When the device is activated, the illuminator 220 may illuminate to indicate to the user that the detector 200 is active, but is not yet at an appropriate use temperature and is therefore not ready to be used. Additionally, when a first temperature (e.g., a breakthrough temperature) outside the standard refrigeration range is detected (which may occur substantially simultaneously with the illuminator 220 being activated), a timer may begin to passively measure the passage of time. Once a prescribed amount of time has passed, the processor 212 (which may include a timer that measures the passage of time) may illuminate the illuminator 208 and deactivate the illuminator 220. By activating the illuminator 208, the detector 200 may indicate to the user that the drug product is within an appropriate use temperature range. In some embodiments, the appropriate use temperature range may correspond to a standard ambient temperature (e.g., room temperature) range of 20° C. to 22° C. In some embodiments, the appropriate use temperature range may be between 15° C. and 30° C., depending at least on the API of the drug product. In some embodiments, the user may be additionally notified that the drug product is ready for use from an audible indication produced by the speaker 210 and / or via a notification on the GUI 222 of the mobile computing device 218.

[0143] Example relationship between API and container temperature

[0144] Figure 3 An example graph of temperature versus time is illustrated, wherein the temperature of a vessel, the temperature of a liquid contained within the vessel (eg, an API), and ambient room temperature (eg, 21.7° C. in this example) are measured over time. Figure 3The graph of the graph can show the relationship between the temperature of each of the three entities (e.g., liquid, container, and room). In some embodiments, the relationship between at least the temperature of the liquid and the container can be applied within one or more algorithms configured in the detector 200, so that when the detector 200 detects the temperature of the container, as described above, the temperature of the API in the container can be estimated (e.g., inferred) based on the relationship drawn and / or tabulated. As shown in the figure, the temperature of the container and the liquid can increase at substantially the same rate over time, however, the temperature at which the liquid is located may be initially colder due to storage in a controlled cooling environment. Therefore, the container can reach room temperature faster than the liquid, depending on one or more factors, such as the type of liquid, the material of the container, the volume of the liquid, the presence of air gaps, etc. For example, based on the heat capacity of the container (e.g., this depends at least on the mass and specific heat of the container), the rate at which heat is transferred from the surrounding environment to the API through the container can vary. As shown in the figure, the temperature difference between the temperature of the container and the temperature of the liquid can decrease over time. Therefore, in some embodiments, the temperature of the container may not be required to reach the ambient room temperature at which the drug product will be ready to be used. This relationship can be determined and tabulated for a variety of container materials, liquid types, and liquid volumes, for example, for use in an algorithm that determines when a drug product is ready to be used.

[0145] Fluid-Based Detectors for Pharmaceutical Products

[0146] In some embodiments, the above Figure 1 The described detector 100 may be embodied in a fluid-based system including one or more fluids (eg, liquids, gases) that may be selected to detect a change in temperature of a drug product and to travel for a specified duration before indicating whether the drug product is ready for use. FIG. 4A to FIG. 4E Various fluid-based detectors configured to detect the temperature of a pharmaceutical product and indicate whether the pharmaceutical product is ready to be used when a specified amount of time has elapsed are shown in accordance with some embodiments.

[0147] Figure 4A The front end of a fluid-based detector 400 is shown in different stages of use, and the detector 400 is configured to detect the temperature of a drug product and indicate whether the drug product is ready to be used after a specified amount of time has passed. The detector 400 may include the above-mentioned Figure 1 and FIG. 2A to FIG. 2FAny one or more features of the detectors 100, 200 described. For example, the detector 400 can be removably attached to the drug product (e.g., with an adhesive). In some embodiments, due to one or more irreversible features, the detector 400 can be disposable and single-use. The detector 400 may include a user-controlled activator 404, a temperature sensor 406, and an indicator 408. In some embodiments, the user-controlled activator 404 may include a button (e.g., a blister) configured to activate the movement of a fluid contained in a reservoir (e.g., a sealed chamber) associated with the button. The fluid may include a miscible fluid (e.g., a dyed liquid, a gel, etc.). In some embodiments, the temperature of the fluid of the detector 400 may be (e.g., via one or more empirical relationships) related to the temperature of the active pharmaceutical ingredient (API) contained in the drug product, so that the detected temperature of the fluid can be used to determine when the drug product is ready to be used.

[0148] In some embodiments, the temperature sensor 406 and the indicator 408 may each include a window and a reservoir (e.g., a chamber) so that a user can observe the fluid (e.g., liquid) in the reservoir through the window to indicate the state of the detector 400. The windows of the indicator 408 and the temperature sensor 406 may include circular, oval, rectangular, or other shapes. In some embodiments, the windows of the indicator 408 and the temperature sensor 406 may include substantially the same shape; in some embodiments, the window of the temperature sensor 406 may be one shape (e.g., rectangular), and the window of the indicator 408 may be a different shape (e.g., oval).

[0149] As shown, the temperature sensor window and the indicator window can be empty (e.g., empty) reservoirs prior to use. Upon activation of the detector 400, fluid can travel from the reservoir associated with the user-controlled activator 404 to the temperature sensor 406 to indicate that the detector is active. For example, the user-controlled activator 404 can be configured to induce pressure in a reservoir containing fluid of the detector 400, such that when the user-controlled activator 404 is pressed or pushed downward (e.g., for 1 second, 2 seconds, 3 seconds, or more), the fluid contained in the reservoir can flow (e.g., via one or more capillaries, as described in connection with the invention) to the temperature sensor 406. FIG. 4B to FIG. 4E406). In some embodiments, the fluid contained in the reservoir associated with the user-controlled activator 404 can be configured to begin traveling toward the temperature sensor 406 upon detecting a temperature change that may affect the state of the fluid (e.g., at the melting point of the fluid, where the fluid changes from a solid to a liquid). After a specified amount of time, the fluid visible in the temperature sensor 406 can travel to the indicator 408 (e.g., via one or more capillaries, substrates, gels, etc.) and be visible in the indicator to indicate that the drug product is ready to be used.

[0150] In some embodiments, temperature sensor 406 may include a label configured to indicate that detector 400 is active, but the drug product is not ready to be used (e.g., "on," "active," "not ready to be used," "not ready," etc.). Similarly, indicator 408 may include a label configured to indicate that the drug product is ready to be used (e.g., "ready," "ready to be used," "ready to use," etc.). Each of the labels may be disposed on and / or adjacent to windows of the sensor and indicator. For example, the label may be disposed on the window such that the label may be illegible when the reservoir associated with the window of the sensor and indicator is empty, and the label may be legible when the reservoir contains fluid. According to some embodiments, the following will be described with respect to FIG. 4B to FIG. 4E The manner in which fluid may travel from the reservoir associated with the user-controlled activator 404 and to each of the reservoirs of the temperature sensor 406 and the indicator 408 is described in greater detail.

[0151] Figure 4BThe rear end of the detector 400 including a fluid reservoir 428 and one or more substrate passages 430, 432 is shown. As described above, the fluid may be configured to travel from the fluid reservoir 428 associated with the user-controlled activator 404 when the detector 400 is activated. In some embodiments, the fluid reservoir 428 may be fluidically connected to the reservoir of the temperature sensor 406 via one or more capillaries (e.g., fluid passages). In some embodiments, the interface between the reservoir 428 and the capillary configured to connect the reservoir 428 to the reservoir of the temperature sensor 406 may include one or more valves (not illustrated). For example, by engaging with the user-controlled activator 404 and thereby causing pressure on the reservoir 428, the valve at the interface may be actuated to allow the fluid contained in the reservoir 428 to travel through the one or more capillaries toward the reservoir of the temperature sensor 406. In some embodiments, the valve at the interface may be actuated when a temperature change (e.g., reaching or exceeding a breakthrough temperature) is detected by the temperature sensor 406. In some embodiments, the time required to travel from the reservoir 428 to the temperature sensor 406 may be negligible and independent of the temperature of the fluid.

[0152] In some embodiments, the fluid may be contained within the reservoir of the temperature sensor 406 until one or more breakthrough temperatures of the fluid are detected. In some embodiments, the fluid in the detector 400 may be selected such that upon detection of a first breakthrough temperature of the fluid (e.g., 10° C., 12° C., 14° C., etc.), at least a portion of the fluid may begin to travel through the first substrate passage 430 (e.g., film, gel, etc.). For example, upon detection of the first breakthrough temperature, a valve between the reservoir of the temperature sensor 406 and the substrate passage 430 may be actuated such that the fluid may travel into the substrate passage 430. In some embodiments, upon detection of a second breakthrough temperature of the fluid (e.g., 16° C., 18° C., 20° C., etc.), at least a portion of the fluid may begin to travel through the second substrate passage 432. For example, upon detection of the second breakthrough temperature, a valve between the reservoir of the temperature sensor 406 and the substrate passage 432 may be actuated such that the fluid may travel into the substrate passage 432. In some embodiments, each of the first substrate passage 430 and the second substrate passage 432 can be configured such that the fluid can travel through these passages within a specified amount of time. For example, the fluid can travel through the first substrate passage 430 within a first specified amount of time (e.g., 50 minutes) and travel through the second substrate passage 432 within a second specified amount of time (e.g., 10 minutes). Thus, in the event that a second (e.g., higher) breakthrough temperature is detected, the fluid can begin to travel through the second substrate passage 432, which can require less time to reach the indicator 408.

[0153] In some embodiments, the detector 400 may include multiple substrate pathways configured to correspond to various durations of time that the drug product is ready to be used. For example, in addition to or in lieu of one or more of the substrate pathways described above, the detector 400 may also include a third substrate pathway, wherein the fluid may travel through the third pathway and reach the indicator 408 within a specified amount of time, regardless of the detected temperature.

[0154] The substrate passage may include a porous film, gel, or other material configured to allow a fluid to travel through the passage within a specified amount of time. In some embodiments, the size (e.g., length, width, etc.) of the substrate passage in the detector 400 may be configured to allow the fluid to travel within a specified amount of time. The specified amount of time may correspond to one or more requirements for the use of the drug product. For example, a given API contained in a drug product may need to stand at ambient temperature (e.g., room temperature) for a specified amount of time, and / or may need to reach an appropriate use temperature (e.g., a desired temperature) before using the drug product. Therefore, one or more substrate passages 430, 432 may be configured to correspond to the required amount of time, or in some embodiments, may be configured so that when the fluid reaches the indicator 408, the API will be at the desired use temperature.

[0155] In some embodiments, the fluid may be contained within the reservoir of the temperature sensor 406 for a negligible amount of time before traveling into the one or more substrate passages 430, 432. For example, when the fluid reservoir of the temperature sensor 406 reaches a threshold pressure, one or more valves at the interface between the temperature sensor 406 and the one or more substrate passages 430, 432 may be actuated to allow the fluid to travel into the passages. In some embodiments, as described above, the fluid may travel through the one or more substrate passages 430, 432 within a specified amount of time. In some embodiments, the specified amount of time may be independent of the temperature of the fluid.

[0156] In some embodiments, the fluid may be contained within the reservoir of the temperature sensor 406 until the breakthrough temperature is reached or exceeded. Upon reaching the breakthrough temperature, the fluid of the detector 400 may travel (e.g., via one or more capillaries, etc.) into the indicator 408. For example, the breakthrough temperature may indicate that the drug product is ready to be used, so the fluid may travel from the temperature sensor 406 to the indicator 408 in a negligible amount of time (e.g., the fluid pathway fluidly connecting the indicator may not act as a timing mechanism).

[0157] In some embodiments, one or more substrate pathways 430, 432 may be fluidly connected to an indicator 408. As described above, the indicator 408 may be configured to indicate whether the drug product is ready to be used. Thus, when the fluid of the detector 400 travels through the one or more substrate pathways 430, 432, the fluid may travel to the reservoir of the indicator 408. In some embodiments, once the fluid traveling from the first substrate pathway 430 or the second substrate pathway 432 reaches the reservoir of the indicator 408 (e.g., whichever occurs first), the indicator 408 may indicate when the drug product is ready to be used.

[0158] Figure 4C A fluid-based detector 400 is shown that includes more than one fluid. In some embodiments, the fluid of the reservoir 434 can be different from the fluid of the reservoir 428, such that the two separate fluids are configured to travel to the temperature sensor 406, for example, upon reaching or exceeding different breakthrough temperatures. For example, upon activation via the user-controlled activator 404 (described in more detail above), the first fluid (e.g., the fluid in the reservoir 428) can be configured to travel to the temperature sensor 406 upon reaching a first breakthrough temperature (e.g., 10° C., 12° C., 14° C., etc.). Similarly, upon activation via the user-controlled activator 404, the second fluid (e.g., the fluid in the reservoir 434) can be configured to travel to the temperature sensor 406 upon reaching a second breakthrough temperature (16° C., 18° C., 20° C., etc.) (e.g., whichever occurs first). In some embodiments, the fluid in the reservoir 428 can travel at a first rate, and the fluid in the reservoir 434 can travel at a second rate, the rates depending on the detected temperature. The fluid from the reservoirs 428, 434 may be Figure 4B The depicted approach proceeds from temperature sensor 406 to indicator 408 to indicate when the drug product is ready to be used.

[0159] In some embodiments, the substrate pathways of detector 400 may be embodied in a variety of configurations. The configuration of each of the substrate pathways may be selected to correspond to a specified amount of time, such that the time required to travel through a given substrate pathway corresponds to the amount of time required for the drug product to be ready for use. Figure 4DA detector 400 is shown that includes one or more gel-filled fluid passages 436, 438 configured to convey the fluid of the detector from a temperature sensor 406 to an indicator 408 to indicate whether the drug product is ready to be used. In some embodiments, one or more properties of the fluid passages 436, 438 may be varied to correspond to the amount of time required for the drug product to reach the desired temperature. In some embodiments, the properties of the fluid passages 436, 438 may be varied to correspond to the amount of time that the drug product must rest outside a controlled cooling environment before use. For example, the length, width, configuration, and type of the gel in the passages 436, 438 may be manipulated to correspond to one or more prescribed amounts of time. In some embodiments, the interface between the temperature sensor 406 and the one or more passages 436, 438 may include one or more valves so that the one or more valves may be actuated when reaching or exceeding one or more breakthrough temperatures to allow the fluid to travel to the indicator 408. In some embodiments, the fluid can be configured to travel from the temperature sensor 406 and into the one or more gel-filled passages 436, 438 when a threshold pressure amount is reached due to the fluid traveling from the fluid reservoir 428 to the temperature sensor 406 after activation (e.g., via a user-controlled activator 404), rather than requiring reaching or exceeding a breakthrough temperature. In some embodiments, the detector 400 can include one or more exhaust paths 440. The exhaust paths can be configured to assist in the circulation of the fluid in the detector 400 by providing a path into which the remaining gel of the passage that does not interact with the fluid of the detector 400 can enter as the fluid travels through the one or more gel-filled fluid passages toward the indicator 408. For example, as Figure 4D As shown, the exhaust path may fluidly connect the reservoir of the indicator 408 to the reservoir 428 associated with the user-controlled activator 404 .

[0160] In some embodiments, detector 400 may include more than one fluid configured to interact with each other and indicate whether a drug product is ready to be used. Figure 4EA detector 400 including a gas and a fluid (e.g., a liquid, a gel, etc.) is illustrated. In some embodiments, the gas may be contained within a reservoir 428 associated with a user-controlled activator 404, such that upon activation, the gas may travel from the reservoir 428 (e.g., due to pressure induced in the reservoir 404) and through one or more capillaries toward the temperature sensor 406. In some embodiments, one or more capillaries of the reservoir fluidly connecting the reservoir 428 and the temperature sensor 406 may include a fluid (e.g., a liquid, a gel, etc.), such that upon activation of the detector 400, the gas may cause the fluid to travel from the capillaries and into the temperature sensor 406 to indicate that the detector 400 is active. In some embodiments, the temperature sensor 406 may be fluidly connected to the indicator 408 via one or more substrate passages 430 (e.g., capillaries). The fluid of detector 400 can travel from temperature sensor 406 to indicator 408 within a specified amount of time, which is configured, for example, to correspond to the amount of time required for the drug product to rest before use. In some embodiments, the specified amount of time can be configured to correspond to the amount of time required for the drug product to reach an appropriate use temperature.

[0161] In some embodiments, the detector 400 may include one or more valves, for example, at the interface between the reservoir 428 and the capillary that fluidly connects the reservoir to the temperature sensor 406. Thus, when the user activates the detector 400, the gas contained in the reservoir associated with the user-controlled actuator 404 may be configured to actuate the valve to allow the gas to travel into the capillary. In some embodiments, the interface between the capillary and the temperature sensor 406 may instead or additionally include a valve that is configured to be actuated when the gas enters the capillary and increases the pressure in the capillary, so that the fluid in the capillary enters the reservoir of the temperature sensor 406 through the valve. In some embodiments, one or more valves may be actuated when one or more breakthrough temperatures of the fluid are detected. In some embodiments, when the breakthrough temperature is reached or exceeded, the fluid may begin to travel from the temperature sensor 406 toward the indicator 408. In some embodiments, the detector 400 may include one or more vents configured to allow any trapped gas of the detector 400 to leave. For example, vent 440 may be fluidly connected to a reservoir of indicator 408 such that gas may be released from vent 440 as fluid (eg, liquid, gel, etc.) travels through one or more reservoirs of detector 400 toward the reservoir of indicator 408 .

[0162] Liquid crystal sensors for pharmaceutical products

[0163] In some embodiments, the above Figure 1The described detector 100 may be embodied in a liquid crystal (eg, thermochromic) sensor that includes liquid crystals that can detect changes in temperature of a pharmaceutical product and change color to indicate whether the pharmaceutical product is ready to be used. FIG. 5A to FIG. 5H Various liquid crystal sensors configured to detect the temperature of a pharmaceutical product and indicate whether the pharmaceutical product is ready to be used are shown according to some embodiments.

[0164] Figures 5A to 5H A liquid crystal sensor 500 is shown that is configured to detect a temperature change of a drug product and indicate when the drug product is ready to be used. For example, a liquid crystal disposed on a polymer may be configured to change color at a specified temperature and / or time to indicate whether the drug product is ready to be used. In some embodiments, the liquid crystal sensor 500 may include the liquid crystal sensor described above with respect to Figure 1 , FIG. 2A to FIG. 2F and / or FIG. 4A to FIG. 4E Any one or more features of detectors 100, 200 and / or 400 as described.

[0165] like Figure 5A As shown, the liquid crystal sensor 500 may include a first indicator 520 configured to indicate whether the drug product is not ready to be used, and a second indicator 508 configured to indicate whether the drug product is ready to be used. In some embodiments, one or more of the first indicator and the second indicator may include liquid crystals configured to detect the temperature of the drug product and change color as the temperature of the drug product increases (e.g., warms up). In some embodiments, the liquid crystals of the liquid crystal sensor 500 may be configured so that they resemble a meter when changing color, such as Figure 5A As shown. Indicator 508 can be configured to correspond to a portion of the meter that can illustrate whether the drug product is ready to be used. For example, indicator 508 can include a colored mark that can separate a first portion of the meter (e.g., when the drug product is not ready to be used) from a second portion of the meter (e.g., when the drug product is ready to be used). In some embodiments, indicator 508 can additionally or instead include an icon (e.g., a check mark, a thumbs-up, a text label, etc.) that is disposed adjacent to and / or within the second portion of the meter to indicate whether the drug product is ready to be used.

[0166] In some embodiments, the liquid crystal can be configured to first change color at one end of the meter within the first indicator 520 when the drug product with the liquid crystal sensor 500 attached thereto is removed from a controlled cooling environment (e.g., a refrigerator, freezer, etc.). As the drug product continues to warm to an appropriate use temperature (e.g., ambient temperature), additional liquid crystals of the sensor 500 can change color to "fill in" the meter. For example, as the detected temperature increases, the liquid crystal between that end of the meter within the indicator 520 and the second indicator area 508 can change color over time. After a specified time has passed and / or if the ambient temperature is detected, the liquid crystal associated with the second indicator 508 can be configured to change color to indicate that the drug product is ready to be used.

[0167] Figure 5B A liquid crystal sensor 500 is shown that includes a first indicator 520 configured to indicate whether a drug product is not ready to be used, and a second indicator 508 configured to indicate whether a drug product is ready to be used. Figure 5A The sensor 500 described, one or more of these indicators may include liquid crystal. For example, the liquid crystal within the indicator 520 may be configured to "fill" the gauge visualization as the temperature of the detected drug product warms up. The liquid crystal may be configured to change color in a continuous mode so that the gauge fills over time in a direction toward the second indicator 508. In some embodiments, the second indicator 508 may include a colored frame configured to indicate a portion of the gauge that may correspond to when the drug product is ready to be used. For example, when the liquid crystal set in the frame of the indicator 508 changes color, the drug product may be ready to be used. In some embodiments, the frame of the indicator 508 may be permanently visible (e.g., may not include a liquid crystal configured to change color based on the detected temperature). In some embodiments, the indicator 508 may be emphasized in a color different from the color of the liquid crystal (e.g., the liquid crystal of the exemplified gauge may be red, and the indicator 508 may be green). In some embodiments, the indicator 508 may include a label configured to inform a user that the drug product is ready to be used when a liquid crystal disposed within the indicator 508 changes color (eg, "READY," "READY TO USE," etc.).

[0168] In some embodiments, the liquid crystal sensor may additionally provide one or more of the expected injection time, the detected temperature of the drug product, the time when the drug product will be ready for use, etc. For example, Figure 5CThe illustrated liquid crystal sensor 500 may indicate when the drug product is not ready for use with one or more of an icon and / or a text field, and after a certain time has elapsed, may indicate that the drug product is ready for use (508) in addition to one or more injection times 542. For example, in the case of injecting an API at a low temperature (e.g., high viscosity) before the drug product reaches an appropriate use temperature, the first injection time may correspond to the amount of time used to inject the API. In the case of injecting the API at an appropriate use temperature, the second displayed injection time may correspond to the amount of time used to inject the API (e.g., the injection time may be estimated and displayed in advance of the time when the API is to be injected).

[0169] same, Figure 5D A liquid crystal sensor 500 is shown that includes an indication (e.g., an icon and / or text field) 520 of when a drug product is not ready to be used, in addition to a meter that is configured to dynamically update to display an injection speed (542). In some embodiments, the meter may be displayed on the liquid crystal sensor 500 at all times, and the indicator on the meter may be configured to move (e.g., the liquid crystal may change color) based on the detected temperature. For example, as the drug product heats up, the indicator may move from the "slow" end of the meter to the "fast" end of the meter to indicate that the injection time (e.g., rate) is increasing. Figure 5D As shown, when the drug product is ready to be used, the liquid crystal (520) that previously indicated the status of the drug product can be configured to change color, and the liquid crystal sensor 500 can display the expected injection rate of the API.

[0170] Figure 5E A liquid crystal sensor 500 is shown including a plurality of indicators (e.g., graphics, icons, etc.) configured to indicate whether a drug product is ready to be used. For example, as the liquid crystal sensor 500 detects a change in the temperature of the drug product, the liquid crystals constituting the indicators may change color (e.g., fade out) over time until the detector is completely free of indicators. When the indicator 520 disappears, the drug product may be ready to be used.

[0171] Fig. 5FA liquid crystal sensor 500 is shown including an indicator 520 that is configured to indicate that a drug product is not ready to be used. For example, the indicator 520 may include an empty icon (e.g., an outline of a shape such as a circle, square, oval, star, triangle, etc.). As the liquid crystal detects a temperature change, the empty icon may be configured to change color and / or fill, as illustrated by the indicator 508. For example, the indicator may change from a first color (e.g., red) to a second color (e.g., green). The indicator 508 configured to indicate that a drug product is ready to be used may additionally include one or more ubiquitous icons (e.g., thumbs up, star, check mark, etc.) that may appear when the drug product is ready to be used.

[0172] Figure 5G Shown includes the above FIG. 5A to FIG. 5B One or more characteristics of a liquid crystal sensor. For example, Figure 5G The liquid crystal sensor 500 illustrated in FIG. 5 may include a meter having a first portion / end (520) configured to indicate when a drug product is not ready to be used and a second portion / end (508) configured to indicate when the drug product is ready to be used. In some embodiments, as the detected temperature increases, the liquid crystal comprising the meter may dynamically change color over time from the first end to the second end to indicate when the drug is about to be prepared and / or ready to be used.

[0173] Figure 5H A liquid crystal sensor is shown that is configured to indicate when a drug product is ready to be used and to transmit information about the temperature of the product as the drug product heats up. For example, the liquid crystal sensor 500 may include a scale in which a temperature reference is indicated, so that at a first end (520) of the scale, low temperatures may be displayed as they are detected. After a certain time has passed, the temperature reference on the second end of the scale (e.g., corresponding to when the drug product is ready to be used) may be gradually displayed. In some embodiments, the appropriate use temperature (e.g., outlined with an indicator 520) may be emphasized to indicate when the drug product is ready to be used.

[0174] The above article about FIG. 5A to FIG. 5H Each of the described liquid crystal sensors 500 may include one or more features described with respect to another embodiment. Figure 5A The detector 500 described may include Figure 5H One or more features of the described detector 500 (e.g., Figure 5AThe detector 500 may additionally display temperature information). The various embodiments and figures of the liquid crystal sensor 500 are not intended to be interpreted as separate embodiments, but rather illustrate a variety of features that may be implemented in combination using liquid crystal (e.g., thermochromic) sensing to at least indicate when a drug product is ready to be used.

[0175] Color-changing materials for pharmaceutical products

[0176] In some embodiments, the above Figure 1 One or more components of the described detector 100 may be embodied within the drug product itself. For example, a container for a drug product may include one or more color-changing materials configured to detect the temperature of the drug product and change color when the drug product is at an appropriate use temperature. In some embodiments, the color-changing material of the drug product may be configured to change color for a specified duration so that the drug product is ready to be used when a specified amount of time has passed. In some embodiments, the rate at which the color-changing material of the drug product changes color may be selected based on one or more properties (e.g., type, volume, etc.) of the API contained within the drug product.

[0177] In some embodiments, the container of the drug product may include a window (e.g., on a syringe holder) that is configured to change color at an appropriate use temperature. In some embodiments, the window may additionally or instead change color after a prescribed amount of time has passed after the drug product has been taken out of a refrigerator. In some embodiments, the window may change from opaque to transparent, or vice versa. In some embodiments, the additional or different components of the drug product may be configured to change color when appropriate use temperature and / or prescribed amount of time have passed. For example, the cap of an automatic syringe may be configured to change from opaque to transparent (or vice versa) when the drug product is ready to be used.

[0178] In some embodiments, one or more components of the drug product may include a color-changing polymer. For example, in the case where the container of the drug product is a drug delivery device (e.g., a syringe), the needle guard of the device may be configured to change color when the drug product is ready to be used (e.g., based on reaching one or more of temperature and / or time). In some embodiments, the piston of the drug delivery device may be additionally or alternatively configured to change color when the drug product is ready to be used. In some embodiments, one or more internal components of the drug delivery device may change color when the drug product is ready to be used, and the user may observe the internal color-changing components through a window (e.g., on the syringe holder).

[0179] In some embodiments, the drug product may include any combination of the detection systems described above. For example, the drug product may include a liquid crystal sensor configured to display the injection time and one or more color-changing materials configured to indicate when the drug product is ready to be used. In some embodiments, the drug product may include one or more illuminators (e.g., LED light indicators) and an LED display configured to display the injection time. The examples provided are not intended to be limiting, and it should be understood that any combination of the features of the detection systems described herein may be combined to at least indicate when the drug product is ready to be used.

[0180] Methods of indicating that a drug product is ready for use

[0181] As described above, the detectors disclosed herein may be configured to be attached to a drug product and may detect the temperature of the drug product and indicate when the drug product is ready to be used.The drug product may include a container configured to hold an active pharmaceutical ingredient (API). Figure 6 A method 600 for detecting the temperature of a pharmaceutical product and indicating when the pharmaceutical product is ready to be used is shown according to some embodiments.

[0182] At step 602, a temperature sensor of the detector may detect the temperature of the drug product. At step 604, at least one timer of the detector may begin measuring the passage of time when the detected temperature of the drug product reaches or exceeds the breakthrough temperature. In some embodiments, as described above, the timer may be embodied in a processor of the detector. At step 606, at least one indicator of the detector may generate an indication that the drug product is ready to be used when a specified amount of time has passed on at least one timer. In some embodiments, the specified amount of time may be selected to correspond to when the API contained in the drug product will be ready to be used. In some embodiments, the specified amount of time may be selected to correspond to the amount of time that the API contained in the drug product will reach the desired temperature when it is set in an environment within a standard room temperature range.

[0183] The above description sets forth exemplary systems, methods, techniques, parameters, etc. However, it should be recognized that such description is not intended as a limitation on the scope of the present disclosure, but is provided as a description of exemplary embodiments.

[0184] Although the description herein uses the terms first, second, etc. to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another.

Claims

1. A detector configured to be attached to a pharmaceutical product containing an active pharmaceutical ingredient (API) therein, the detector comprising: a temperature sensor configured to detect a temperature of the drug product; at least one timer configured to begin measuring the passage of time if the temperature of the drug product detected by the temperature sensor reaches or exceeds a breakthrough temperature; as well as At least one indicator is configured to generate an indication that the pharmaceutical product is ready to be used if a specified amount of time has elapsed on the at least one timer.

2. The detector of claim 1, wherein the specified amount of time is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

3. A detector according to any one of claims 1 to 2, wherein the specified amount of time is selected to correspond to the amount of time it will take for the active pharmaceutical ingredient (API) contained within the drug product to reach a desired temperature when placed in an environment within a standard room temperature range.

4. The detector according to any one of claims 1 to 3, wherein the breakthrough temperature corresponds to a temperature outside a standard refrigeration temperature range.

5. A pharmaceutical product, comprising: a container configured to hold an active pharmaceutical ingredient (API); as well as A detector according to any one of claims 1 to 4, wherein the detector is arranged adjacent to the container.

6. The drug product of claim 5, wherein the container comprises a syringe configured to contain the active pharmaceutical ingredient (API).

7. The drug product of claim 6, wherein the injector comprises an autoinjector.

8. The pharmaceutical product of any one of claims 5 to 7, wherein the temperature sensor determines the temperature of the active pharmaceutical ingredient (API) based at least in part on the temperature of the container.

9. A pharmaceutical product according to any one of claims 5 to 8, wherein the detector is removably attached to the container.

10. The detector of any one of claims 1 to 9, comprising a user controlled activator configured to activate the temperature sensor.

11. The detector according to any one of claims 1 to 10, wherein the at least one timer is configured to start measuring a second time lapse if the temperature of the drug product detected by the temperature sensor reaches or exceeds a second breakthrough temperature.

12. The detector of claim 11, wherein the second breakthrough temperature is greater than the breakthrough temperature.

13. The detector according to any one of claims 11 to 12, wherein a first timer of the at least one timer is configured to measure the time lapse when the breakthrough temperature is detected, and a second timer of the at least one timer is configured to measure the second time lapse when the second breakthrough temperature is detected.

14. The detector according to any one of claims 11 to 13, wherein the time lapse measured by the at least one timer is of a longer duration than the second time lapse measured by the at least one timer.

15. The detector of any one of claims 11 to 14, wherein the at least one indicator is configured to generate the indication that the pharmaceutical product is ready to be used if a second prescribed amount of time has elapsed on the at least one timer.

16. The detector of any one of claims 1 to 15, wherein the at least one indicator comprises at least one of an audio indicator and / or a visual indicator.

17. The detector of claim 16, wherein the visual indicator comprises a first illuminator configured to be activated when the pharmaceutical product is ready to be used.

18. The detector of claim 17, wherein the visual indicator comprises a second illuminator configured to be activated if the pharmaceutical product is not ready for use.

19. A detector according to any one of claims 16 to 18, wherein the audio indicator is configured to produce a sound if the pharmaceutical product is ready to be used.

20. The detector of any one of claims 1 to 19, wherein the indicator comprises a graphical user interface (GUI) on a mobile device, the graphical user interface (GUI) configured to indicate when the pharmaceutical product is ready to be used.

21. The detector of claim 20, wherein the mobile device is communicatively coupled to one or more of the temperature sensor and the timer.

22. The detector of any one of claims 20 to 21, wherein the graphical user interface (GUI) is configured to display an expected duration for an injection based at least in part on the detected temperature and the drug product.

23. The detector of any one of claims 1 to 22, comprising a fluid configured to travel through the temperature sensor and the at least one timer.

24. The detector of claim 23, comprising a user-controlled activator configured to cause the fluid to travel from a reservoir associated with the user-controlled activator and to the temperature sensor when the user-controlled activator is activated.

25. The detector of claim 24, wherein the temperature sensor comprises a window configured to indicate that the detector is active.

26. The detector of any one of claims 24 to 25, wherein the fluid is configured to travel from the temperature sensor and through the at least one timer if the drug product reaches or exceeds the breakthrough temperature.

27. The detector of claim 26, wherein the fluid is configured to travel through the at least one timer and to the at least one indicator within the specified amount of time.

28. The detector of claim 27, wherein the specified amount of time corresponds to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

29. The detector of any one of claims 27 to 28, wherein the fluid is configured to travel from the temperature sensor and through a second timer of the at least one timer if the drug product reaches or exceeds a second breakthrough temperature.

30. The detector of claim 29, wherein the fluid is configured to travel through the second timer and to the at least one indicator within a second specified amount of time.

31. The detector of claim 30, wherein the second breakthrough temperature is greater than the breakthrough temperature, and wherein the second prescribed amount of time is greater than the prescribed amount of time.

32. A method of indicating that a pharmaceutical product is ready for use, the method comprising: detecting the temperature of the drug product with a temperature sensor; measuring the passage of time with at least one timer when the temperature of the drug product detected by the temperature sensor reaches or exceeds a breakthrough temperature; as well as An indication that the drug product is ready for use is generated using at least one indicator and when a specified amount of time has elapsed on the at least one timer.

33. The method of claim 32, wherein the specified amount of time is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

34. The method of any one of claims 32 to 33, wherein the specified amount of time is selected to correspond to an amount of time that the active pharmaceutical ingredient (API) contained within the drug product will reach a desired temperature when placed in an environment within a standard room temperature range.

35. A method according to any one of claims 32 to 34, wherein the breakthrough temperature corresponds to a temperature outside the standard refrigeration temperature range.

36. A method according to any one of claims 32 to 35, comprising activating the temperature sensor with a user controlled activator.

37. A method according to any one of claims 32 to 36, comprising measuring a second lapse of time with the at least one timer if the temperature of the drug product detected by the temperature sensor reaches or exceeds a second breakthrough temperature.

38. The method of claim 37, wherein the second breakthrough temperature is greater than the breakthrough temperature.

39. The method of any one of claims 37 to 38, wherein a first timer of the at least one timer is configured to measure the time lapse if the breakthrough temperature is detected, and a second timer of the at least one timer is configured to measure the second time lapse if the second breakthrough temperature is detected.

40. The method of any one of claims 37 to 39, wherein the lapse of time measured by the at least one timer is of a longer duration than the second lapse of time measured by the at least one timer.

41. A method according to any one of claims 37 to 40, comprising generating the indication that the drug product is ready for use with the at least one indicator and when a second prescribed amount of time has elapsed on the at least one timer.

42. The method of any one of claims 32 to 41, wherein the at least one indicator comprises at least one of an audio indicator and / or a visual indicator.

43. The method of claim 42, comprising activating the at least one visual indicator if the pharmaceutical product is ready to be used.

44. The method of claim 43, comprising activating a second of the at least one visual indicator if the pharmaceutical product is not ready for use.

45. A method according to any one of claims 42 to 44, comprising activating the audio indicator to produce a sound if the pharmaceutical product is ready to be used.

46. ​​A method according to any one of claims 32 to 45, comprising indicating on a graphical user interface (GUI) on a mobile device that the pharmaceutical product is ready for use.

47. The method of claim 46, wherein the mobile device is communicatively coupled to one or more of the temperature sensor and the timer.

48. The method of any one of claims 46 to 47, comprising displaying on the graphical user interface (GUI) an expected duration for an injection based at least in part on the detected temperature and the drug product.

49. The method of any one of claims 32 to 48, comprising a fluid configured to travel through the temperature sensor and the at least one timer.

50. The method of claim 49, comprising causing the fluid to travel with a user-controlled activator from a reservoir associated with the user-controlled activator and to the temperature sensor.

51. The method of claim 50, wherein the fluid travels from the temperature sensor and through the at least one timer in the event that the drug product reaches or exceeds the breakthrough temperature.

52. The method of claim 51, wherein the fluid travels through the at least one timer and reaches the at least one indicator within the specified amount of time.

53. The method of claim 52, wherein the specified amount of time corresponds to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

54. The method of any one of claims 52 to 53, wherein in the event that the drug product reaches or exceeds a second breakthrough temperature, the fluid travels from the temperature sensor and through a second timer of the at least one timer.

55. The method of claim 54, wherein the fluid travels through the second timer and reaches the at least one indicator within a second specified amount of time.

56. The method of claim 55, wherein the second breakthrough temperature is greater than the breakthrough temperature, and wherein the second prescribed amount of time is greater than the prescribed amount of time.

57. A detector configured to be attached to a pharmaceutical product having an active pharmaceutical ingredient (API) contained therein, the detector comprising: a temperature sensor configured to detect a temperature of the drug product; at least one processor configured to calculate changes between the detected temperatures over time; as well as At least one indicator configured to generate an indication that the pharmaceutical product is ready for use if the calculated change in the change between the detected temperatures over time meets or falls below a predefined threshold.

58. A detector according to claim 57, wherein the predefined threshold is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

59. A detector according to any one of claims 57 to 58, wherein calculating the change between detected temperatures over time comprises determining a difference between a first temperature and a second temperature, the first temperature and the second temperature being detected a predefined amount of time apart.

60. The detector of claim 59, wherein the at least one processor is configured to generate a ratio of the difference between the first temperature and the second temperature to the predefined time interval amount, and compare the ratio to the predefined threshold.

61. A method of indicating that a pharmaceutical product is ready for use, the method comprising: detecting the temperature of the drug product with a temperature sensor; calculating, with at least one processor, changes between the detected temperatures over time; as well as An indication that the drug product is ready for use is generated using at least one indicator and when the calculated change in the change over time between the detected temperatures meets or falls below a predefined threshold.

62. The method of claim 61, wherein the predefined threshold is selected to correspond to when the active pharmaceutical ingredient (API) within the drug product will be ready for use.

63. The method of any one of claims 61 to 62, wherein calculating the change between the detected temperatures over time comprises determining a difference between a first temperature and a second temperature, the first temperature and the second temperature being detected a predefined amount of time apart.

64. The method of any one of claims 61 to 63, wherein the at least one processor generates a ratio of the difference between the first temperature and the second temperature to the predefined time interval amount and compares the ratio to the predefined threshold.

65. A liquid crystal sensor configured to be attached to a pharmaceutical product having an active pharmaceutical ingredient (API) contained therein, the liquid crystal sensor comprising: a liquid crystal configured to change color as the drug product heats up to indicate an increased temperature of the drug product; At least one indicator configured to indicate when the API within the drug product reaches a specified temperature or temperature range, wherein the specified temperature or temperature range indicates when the drug product is ready to be used.

66. The liquid crystal sensor of claim 65, wherein a portion of the liquid crystal is adjacent to the at least one indicator on the liquid crystal sensor and is configured to change color when the drug product is ready to be used.

67. The liquid crystal sensor of any one of claims 65 to 66, wherein the liquid crystal includes a visual meter that indicates the increased temperature of the pharmaceutical product as the pharmaceutical product increases in temperature.

68. The liquid crystal sensor of claim 67, wherein the at least one indicator corresponds to an end of the visual meter.

69. A liquid crystal sensor according to any one of claims 65 to 68, wherein the at least one indicator is configured to indicate an expected duration for an injection.

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