The FDA has released draft guidance: “Regulatory Considerations for Software Related to Prescription Drug Use”, to share the agency’s current thinking on software that accompanies or supplements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

In this CDER conversation, Evan Wearne, PharmD, MS, from the Office of Medical Policy, discusses the role software can play in promoting safe and effective medication use, the intent of the guidance, and future interaction between software and processing.

First things first: what is prescription drug software?

Prescription drug use software is software created by or on behalf of a drug sponsor that supplements, explains, or is otherwise related to a drug. It can potentially provide insight to patients, caregivers, and healthcare providers (collectively referred to as “end users”) about the patient’s use of the medication. It is possible that patients have seen, or even use, this type of software in their daily lives.

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

An example of prescription drug consumption software on the market is a mobile application (app) that acts as a digital medication diary (or digital diary), in which patients manually record and view their medication consumption at over time. The Digital Medication Log does not automatically collect information. 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 product connected to a device. For example, consider medications that provide immediate relief for a condition like asthma, where patients may have sudden attacks. When a patient takes the emergency medication, a piece of hardware connected to the asthma inhaler automatically “counts” the patient’s usage and transmits that measurement 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 healthcare provider through the app. The provider could see how often the patient relied on emergency medications to decide whether the asthma is under control.

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

Would software related to prescription drug consumption be considered digital health technology?

People who follow the digital health space may be wondering what the connection is between prescription drug software and 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 software is a type of digital health technology.

Why did the agency issue these guidelines?

In 2018, the agency comments requested on a possible regulatory framework for software related to prescription drug use, and the FDA wanted to follow up with guidelines to help answer the many questions sponsors have on this topic. Simply put, our goal was to help sponsors understand the regulatory landscape so they could create software to help patients use prescription medications.

From CDER’s perspective, we also wanted to align with other FDA centers, including CDRH, which has published several Digital health policy documents.

This draft guidance specifically addresses how drug sponsors can describe their software in labeling and promotional labeling required by the FDA. Labeling required by the FDA is reviewed and approved by the agency and includes the Prescribing information (PI), a resource for prescribers that contains a summary of essential scientific information needed for the safe and effective use of medicines. 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 of initial labeling release.

For FDA-required labeling, if the sponsor submits evidence that use of the software results in significant improvement in clinical outcomes compared to use of the drug alone, the guidelines recommend that the sponsor include the relevant information in the appropriate IP section(s), such as the “Clinical Studies” section.

CDER recognizes that many sponsors will not have produced data demonstrating clinical benefit with the software. Nonetheless, CDER may determine that the PI must have information about the software, if, for example, the information is needed to inform a prescribing decision, distinguish product versions, or let patients know that the software automatically collects information while using the medicine. In these cases, the guidelines recommend that the sponsor include details of the software in another PI section, such as the “How Provided/Storage and Handling” section.

When will software related to prescription drug use be considered promotional labeling? How should sponsors proceed in this case?

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

As such, Sponsor must follow CDER’s promotional labeling processes and submit the end user result using FDA Form 2253. CDER would review documents produced by the end user to ensure that the information is truthful, non-misleading, and balanced.

A small caveat: where device software functions fall within an appropriate CDRH marketing application, CDRH will review the end user outcome, in consultation with CDER. Sponsors would not need to submit another FDA Form 2253 to CDER for review of promotional labeling.

What is the future of prescription drug software?

The domain is growing! The progress we have seen in the five years since the framework was published is astonishing. While some sponsors add software features to existing therapies as an “optional tool,” others create drugs with digital features to improve safety and effectiveness. These products include new strategies to monitor the effectiveness of drugs or control their distribution. As this trend continues, CDER will continue to monitor the landscape and work with companies to integrate software related to prescription drug use into pharmacy applications. Most importantly, we will help patients, caregivers and healthcare providers leverage these technologies to improve the safe and effective use of prescription medications.