FDA Approves World's First Pill with an Embedded Sensor

You can prescribe a patient medication, but you can't make them take it. Patient compliance has always been an issue in healthcare and one that digital health technologies such as wearables have tried to address. According to The New England Journal of Medicine an estimated 33 to 69 percent of medication-related hospital admissions in the US are due to poor medication adherence, meaning anywhere from about a third to over half of patients are not taking their medications when or as often as they should.

This week the FDA approved a new technology geared toward patient compliance in the form of a prescription pill with a digital sensor embedded in it that lets doctors digitally track just how often a patient is taking his or her medication. The sensor was developed by Proteus Digital Health, a technology company centered around developing what it called “digital medicines,” that combine sensor technology and pharmaceuticals to improve patient outcomes.

The pill in question is Abilify MyCite, a variation of Abilify, a popular medication for treating schizophrenia, bipolar disorder, and some cases of depression, manufactured by Japan-based Otsuka Pharmaceutical. “Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,” Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”

Inside the Digital Pill

Proteus did not respond for requests for comment on the nature of its current pill sensor, but in previous reports with Design News' sister publication MD+DI , company CEO Andrew Thompson laid out the workings of at least an early version. According to Thompson, Proteus' innovation has come from the miniaturization. If you've ever made a lemon or potato battery as a science project, you've seen the basic principle underlying the IEM sensor.

According to a study published in 2015 by Proteus engineers and researchers in IEEE Transactions on Biomedical Engineering, Proteus' sensor, the IEM consists of three layers: an active layer, a 1 mm × 0.3 mm CMOS chip, and an insulation skirt layer, meaning the chip is sandwiched between a layer of magnesium on one side and copper on the other. Thompson reported the IEM silicon wafer as measuring 800 × 300-µm.

After it is swallowed, the sensor comes into contact with the patient's stomach fluid, creating an electrochemical reaction that powers the chip until the electrode materials are fully dissolved. The IEEE study estimated the current at about 1.85 V. Proteus engineers looked at other means for powering the device, such as using electrolyte fluids, however they found the magnesium/copper combination was optimal for biocompatibility (meaning it's safe to ingest), power output, cost, and compatibility with the manufacturing process.

In essence, the sensor is not a mini WIFI, Bluetooth, or radio antenna – it's a detectable power source. The electric signal transmits a binary number that represents the medication and its dosage. The code is stored in the integrated circuit, which modulates the current. The device's insulating skirt shapes the electric field produced by the electrochemical reaction and propagates it through the surrounding tissue, where it can be detected by a skin-worn patch (The MyCite Patch), which records the date and time of the ingestion as well some patient vitals it detects on its own, and can store them on the MyCite's accompanying smartphone app. Using the smartphone app patients can choose who has access to their records, allowing family members and doctors access to check in on them if need be. According to the IEEE study, the electric field emitted by the IEM is similar in nature to ones that occur naturally in the body in the brain, heart, and gastrointestinal tract.

Side Effects Include...

Abilify MyCite does come with warnings however. The IEEE study notes that the power and strength of the signal can depend on a number of factors such the amount of food or even other medications in the patient's stomach. According to Proteus it can take anywhere from 30 minutes to two hours after Abilify MyCite is ingested for the patch to record a signal. And the company admits it is possible that a signal won't be picked up at all.

The FDA has stated, and noted on Abilify MyCite’s labeling, that the product has not been shown to improve patient compliance. Because of the long time delay in picking up a signal, the FDA also states that Abilify MyCite should not be used for real-time tracking or during emergencies. The FDA also warns of side effects associated with the drug itself, including warnings that its effectiveness and safety has not be established with pediatric patients (in most cases symptoms schizophrenia emerge between the ages of 16 and 30).

FDA rejected prior requests for approval from Otsuka Pharmaceutical in 2016 when it sent the company a response letter requesting addition information, including data regarding the performance of Abilify MyCite as well as further human factors testing to ensure that patients could use the pill and its associated devices safely and effectively.

While the Abilify MyCite system is a closed loop (pill, patch, and smartphone app) one has to wonder about the implications of opening up the technology to the wider IoT space. It's not difficult to imagine an in-home network in which you receive reminders to take your medication via some devices in your smart home and then the pill system then letting your home network know you've taken your medication.

The the idea of ingesting a pill that can track you certainly raises some ethical concerns, particularly if the technology advances beyond the binary approach taken by Proteus' engineers. However, the idea of ingestible medical sensors has been around for decades. In the 1980s NASA developed an ingestible thermometer in pill form to help monitor astronauts. A 1991 study in the International Journal of Radiation Oncology*Biology*Physics tested an ingestible temperature sensor for use in treating hypothermia. And in 2015 researchers from MIT published a study describing a proof of concept of an ingestible device that uses tiny microphones to record and transmit sounds from inside the gastrointestinal tract to measure vital signs.

Otsuka is currently doing on a limited roll out of Abilify MyCite. The company said this is a deliberate move to allow it to focus on learning more about patients' experiences with the pill and to allow for ongoing feedback before a larger market release. Proteus did not respond to requests for comment about other drugs that may be candidates for its sensor, but if Abilify MyCite shows good outcomes and is embraced by patients, we can likely expect to see more medications for chronic illnesses getting a digital upgrade as well.  

Chris Wiltz is a Senior Editor at Design News, covering emerging technologies including AI, VR/AR, and robotics.