A combination product’s primary mode of action establishes its regulatory and product development framework as well as how it is viewed in the eyes of a regulator depending on which agency it’s assigned to within the FDA, as we learned from the mini-sim this week. Looking at this digital pill, I would argue the pills primary function is to act as a drug for its prescribed purpose, whether it’s for mental illness (as mentioned in the article) or something else. Since I believe its PMOA is drug related then it would be assigned to The Center for Drug Evaluation and Research (CDER) in the FDA. The aspect of it being able to track whether or not the pill was taken by the user is a secondary feature with the drug portion of the device being the most important in terms of helping the patient and overall purpose of this device in my opinion. With this information a company can prepare to deal with the assigned agency, CDER in this case, to hopefully one day get this product onto the market.

I agree with wms7 -- the pill's primary function is to cause changes in the body biologically and therefore, it would be assigned to the CDER. The sensor does not make actual changes to the body and therefore, is a secondary feature.

Although I think its a really interesting concept, I was actually really interested in two concepts that the article presented:

1. Does the pill present issues of privacy? If the data is transmitted from the sensor to the patch and then to a wireless device, this means that anyone with basic hacking skills might be able to gain access to this information. What issues would this present?
2. Trials using the medication did not indicate that patients were more likely to take their medication with the sensor anymore than they would their regular medication. In addition, it shouldn't be used in case of emergencies because the sensor might not transmit -- in that case, what is the use of this medication?

This medical device is both a device and drug, therefore it is considered a combination product as stated by regulation. The PMOA is too gather a signal of a patient who took their pill or not and monitors metabolic activity. However, there is a drug component that in turn creates biochemical pathway response. Therefore, a RFD (request for designation) had to be filled. With that ruling, CDRH took over as the regulator for this device and was filed as a Class 3 device in which an IDE was done, pivotal trials and PMA was done as well.

The imperative and critical concern is that this device can be an opening another " can of worms" of some menace wanting to hack personal information which can lead to identity thief. Now you have legal and ethical issues that need to be fixed immediately.

After reading few articles about the "digital drug", I think that in one side, its one of the best invention whereas on another side there are some issues which had to be corrected before releasing it into the market. As in the comments above, it is mentioned that it is a concern that people may hack into someone's personal records which is a major drawback of this product. But why will someone hack into someone's record to check if the concerned person has taken his medicine or not? Will the potential hacker get any benefit from that? NO!

One more thing was also mentioned in the article that the device does not give the real time results. There is always a delay in the result. So that needs to be fixed soon too.
In my point of view it is a device that implanted inside a human body so that with some chemical reactions inside the body, it will track if the patient has taken the medication or not.

I think the First Digital Pill in US, Abilify MyCite opens up concerns about patient privacy, but also paves the way for other digital pills. For example, etect Rx is a Florida company that makes another ingestible sensor, the ID-Cap, which has been or is being tested with opioids, H.I.V. medication and other drugs. The company seeks to FDA approval this year.

In a NY Times article the etectRx senior VP, Eric Buffkin,the, says “I get questions all the time, ‘Hey is the government going to use this, and can you track me? Frankly, there is a creepiness factor of this whole idea of medicine tracking. “The thing I tell them first and foremost is there’s nothing to reach out of this technology to pry your mouth open and make you take a pill. If you are fundamentally opposed to this idea of sharing the information, then say, ‘No thank you.’” For Abilify MyCite to address privacy and coercion, Otsuka officials contracted with several bioethicists including I. Glenn Cohen, a Harvard law professor, who says there are safeguards adopted include allowing patients to instantly stop physicians and others from seeing some or all of their data.

I think when technologies are new there is a skepticism and hesitation to adopt, but once they become more popular and rules and regulations/safegaurds are in place, they will become commonplace. In 2018 we are constantly being tracked with our purchasing, apps, and health information. Data is very valuable and I think that this "digital pill" will just be the beginning to more digital pills and regulations that will go along with them. I personally think that if the patient chooses to take digital pills and are aware of the abilities to track and who will be able to see that data that this type of pill could be revolutionary. I agree companies will have to hire bioethicists to make sure patient data is used ethically, but I think the potential benefits outweigh the privacy concerns. Do you think we need to be worried about a Biomedical 'Big Brother'?

nytimes.2017/11/13/health/digital-pill-fda

I think that the primary mode of action of the digital Abilify pill makes it a drug, rather than a device. This digital pill is more of a pill that comes with a sensor than it is a sensor that comes with a pill because the pill most important therapeutic action is the biological action by the drug portion of the combination product. As a combination product whose primary mode of action is a drug the product would be reviewed by CBER.

In my opinion I feel that this is more of a drug then a device. The purpose of this drug used for schizophrenia and act as a sensor second. Patients who are taking the drug are using the sensor to monitor the patients behavior, through the reaction of the drug. Even though the overall goal is for the patients to track their information from the pill to a patch and then the patch sends data to a user's smartphone. I consider this more of a drug because without the pill, this overall purpose is useless. I believe the goal is to make sure the patient is cooperating and taking drug.

Those are two really big issues you brought up. How safe is the data being transmitted? What happens if the sensor is not capable of working? There are cases where sensors do not transmit correct data or do not transmit data at all. In my opinion this device should not be used in emergency. We are not sure how reliable this pill is. That is why I considered this more of a drug then a device. The goal is make sure the drug is helping the patient. The sensor is just used for tracking. What if the patient takes the pill and the sensor does not work. The effects of the pill will continue to have an impact on the patient, however the sensor will not. This is big problem because the sensor becomes secondary. Can you rely on the sensor then?

I believe when deciding the primary mode of action, you should see what is the main function and what is the secondary function. The primary function of the digital pill is to deliver the mental illness medication and the sensor is a secondary and meant to assist the drug delivery. I believe this falls under the CDER department in the FDA. A failure in the sensor is an inconvenience and maybe a waste of money but it is not catastrophic. A failure of the medicine delivering can cause severe damage to the patient and can ultimately lead to a patient hurting themselves or others. The main goal of this pill should be to deliver the drug and therefore it should be in the department that is most suited to make sure that will happen.

While I am not well versed in understanding the rationale of the FDA for determining the PMOA of a device, in this particular case i believe that it is a device. The rationale being that the drug component of the device has already been tested and approved by the FDA and is currently being used to treat patients. The innovative aspect of the device that requires further investigation and validation is the device/monitoring aspect of the product. This becomes increasingly important as patients will be relying on the application to determine when to take their next dose. The risks being too late and the drug wears off or too soon and you have an overdose. The determining factor for a majority of the newly introduced risk lies with the device component of the product.
Another thing to not is that since medical information is being collected and potentially transmitted, HIPPA regulations will apply as well and must be followed before the device can be actually be put on the market.
Now this is a question, I have for you all, does FDA approval mean that the device can now be put on the market or does that only cover the aspects of the device which are regulated by the FDA? In this case patient information.

I would argue that this product is a combination product. Abilify was first approved in 2002 and approved for use to treat Schizophrenia however the new novel aspect of this design is the sensor technology which tracks the ingestion of the pill. This product would elicit a chemical reaction in the body so it could not classify as just a medical device which is what I was tempted to say at first. The primary mode of action would be the sensor technology itself and the transmission of the data to the caregiver. There would need to be extensive testing performed on whether the sensor technology would interfere with the makeup of the drug once embedded into the pill.
Overall this would have to be submitted through a PMA approval process. Since the primary mode of action would be the sensor, it would have to monitored and reviewed by the CDRH. Additionally, since the sensor technology itself is rather novel, it would most likely go to panel where a board can review holistically the effects of the drug and device together rather than as separate entities. I would believe that device would be classified as a class III due to no prior predicates.

In response to ak977, I do believe that those are valid concerns to have over privacy. What I would propose as a potential solution is to have the transmitted data password protected, where the individual sending or receiving the information are the only two with that password to view. We do live in a data dependent society where multiple forms of communication, payments, and important information is transferred electronically. It would be foolish not to implement some form of security to the information that is being transferred. As for your second point, from my understanding the pill is meant for health care professionals to determine whether the medication was actually being taken or not. That would take the lying factor out of the equation where the doctor is well aware if the medication was actually taken or not and can adjust accordingly based of that information. The doctor can determine whether there needs to be additional action taken in order to take the medication.

I agree with aij5. The novel portion of this particular product is the sensor and reporting aspect, the drug is already an approved product. If the device portion is approved it has the potential to be used with other drugs. However, if the device somehow controlled the dosage administered to the patient then there would be more hurdles to cross from a review standpoint. As it stands now the main purpose of the device is to communicate that a patient has taken their medication and it supposedly does not significantly alter the metabolism of the drug in any way.

With the standard pill, not containing the event marker, there were 6 clinical trials done to get the drug approved. With the addition of the marker the new combination product required new clinical trials using the prior 6 trial data sets in addition to one more trial that showed the ability of the patient to use the system successfully. If you read the limitations of usage section and the disclaimer you will see that there may be a delay or the pill may not even register at all, that the ability of the drug to improve patient compliance has not been established, and that it should not be used to monitor real time or in an emergency. From my understanding the only theoretical upside that this sensor embedded drug has is that it allows caretakers and patients to track IF they have taken the pill, to prevent a person from going off their meds or to prevent double dosages in patients who are forgetful. According to the disclaimer and the CDER clinical review this device does not reliably perform that task, what good is a sensor that doesn't reliably sense? It's really only effective as a drug, the device portion is just trivial. I understand that the company covered their behinds by adding the disclaimer so that they aren't claiming something that they cant provide, but how can you put a product out that implies it can perform a certain task and then add a disclaimer that says it probably cant perform the task and you shouldn't rely on this product performing the task successfully. How is this right?