FDA has released a draft guidance, “Regulatory Considerations for Prescription Drug-Use-Related Software,” to share the agency’s current thinking on software that accompanies or supplements prescription drugs.

In this CDER Conversation, the Office of Medical Policy’s Evan Wearne, PharmD, MS, explains the role that software may play in promoting safe and effective drug use, the intent of the guidance, and the future interplay between software and therapeutics.

First things first: What is prescription drug-use-related software?

Prescription drug-use-related software is software made by or on behalf of a drug sponsor that supplements, explains, or is otherwise related to a drug. It may potentially provide insight to patients, caregivers, and health care providers (collectively known as “end-users”) about the patient’s use of the drug. There is a chance that patients may have seen, or are even using, this type of software in their daily lives. 

So far, we have mostly seen products with basic software functions designed for convenience. In the longer term, software could possibly help people take their medications more safely and effectively.

One example of prescription drug-use-related software on the market is a mobile application (app) that acts as a digital medication log (or digital diary), where patients manually record and view their medication use over time. The digital medication log does not collect information automatically. Instead, it relies on people, namely patients or caregivers, to enter data into the app.

Another type of software on the market transmits drug use data directly through a device-connected product. For instance, consider medications that provide immediate relief for a disease like asthma, where patients can have sudden attacks. When a patient takes the emergency medication, a piece of hardware attached to the asthma inhaler automatically “counts” the patient’s usage and transmits that metric to an app on their smartphone. Patients can also choose to share the information (i.e., the number of times they used the inhaler) with their health care provider through the app. The provider could view how often the patient relied on the emergency medication in deciding whether the asthma is under control.

In the asthma example, the prescription drug-use-related software is considered “device-connected.” As a drug-led, drug-device combination product, the asthma medication would fall under CDER’s regulatory purview, in consultation with the Center for Devices and Radiological Health (CDRH).

Would prescription drug-use-related software be considered a digital health technology?

People following the digital health space may be wondering how prescription drug-use-related software relates to digital health technologies. In general, digital health technologies are systems that use computing platforms, connectivity, software and/or sensors for health care and related uses. So yes, prescription drug-use-related software is a type of digital health technology.

Why did the agency put out this guidance?

In 2018, the agency solicited comments on a possible regulatory framework for prescription drug-use-related software, and FDA wanted to follow up with a guidance to help answer the many questions sponsors have on this topic. Simply put, we aimed to help sponsors understand the regulatory landscape so these sponsors could make software to help patients use prescription drugs.

From CDER’s perspective, we also wanted to align with other FDA centers, including CDRH, which has released several recent Digital Health Policy Documents. 

This draft guidance specifically addresses how drug sponsors can describe their software in FDA-required labeling and promotional labeling. FDA-required labeling is reviewed and approved by the agency and includes the Prescribing Information (PI), a resource for prescribers that contains a summary of the essential scientific information needed for safe and effective drug use. Meanwhile, promotional labeling is generally any labeling other than FDA-required labeling and is intended to promote or advertise the drug. Sponsors must submit promotional labeling to CDER at the time the labeling is initially disseminated.

For FDA-required labeling, if the sponsor submits evidence that using the software results in a meaningful improvement in clinical outcome compared to using the drug alone, the guidance recommends that the sponsor include the relevant information in appropriate PI section(s), such as the “Clinical Studies” section.

CDER recognizes that many sponsors will not have produced data to demonstrate a clinical benefit with the software. Still, CDER may determine the PI should have information about the software, if, for example, the information is necessary to inform a prescribing decision, distinguish between product versions, or let patients know that the software is automatically collecting information during drug use. In these cases, the guidance recommends that the sponsor include language about the software in another PI section, such as the “How Supplied/Storage and Handling” section.

When would prescription drug-use-related software be considered promotional labeling? How should sponsors proceed in that case?

Sometimes, especially with software that is not device-connected, CDER does not believe the software provides essential information related to safe and effective medication use. In these cases, it should not be mentioned in the PI. However, the “end-user output” that the software generates — such as a screen display, text message, or audio file — would be considered promotional labeling.

As such, the sponsor must follow CDER’s processes for promotional labeling and submit the end-user output using Form FDA 2253. CDER would review the end-user output material to make sure the information is truthful, non-misleading, and balanced.

A quick caveat: When device software functions fall under an appropriate CDRH marketing application, CDRH would review the end-user output, in consultation with CDER. Sponsors would not need to submit another Form FDA 2253 to CDER for promotional labeling review.

What is the future of prescription drug-use-related software?

The field is growing! The progress we’ve seen in the five years since we released the framework is astonishing. While some sponsors are adding software functions to existing therapies as an “optional tool,” other sponsors are creating drugs with accompanying digital features to improve safety and efficacy. These products include novel strategies to monitor drug efficacy or control dispensing. As this trend continues, CDER will keep monitoring the landscape and will work with companies on incorporating prescription drug-use-related software into drug applications. Most importantly, we will help patients, caregivers, and health care providers leverage these technologies to enhance the safe and effective use of prescription drugs.