USFDA Guidance on Regulatory Considerations for Prescription Drug Use-Related Software
The US Food and Drug Administration (FDA) has issued Regulatory Considerations for Prescription Drug Use-Related Software, a guidance for industry addressing the application of drug labeling requirements to software developed or distributed by, or on behalf of, prescription drug sponsors. The guidance explains how FDA considers software-generated content presented to patients, caregivers, and healthcare professionals, and how this content should be addressed in prescription drug labeling.
The guidance covers software used with prescription drugs and certain drug-device combination products, including mobile applications and web-based tools. It explains how sponsors should determine whether software output constitutes FDA-required labeling or promotional labeling, when software functions should be described in the Prescribing Information (PI), and when end-user output should be submitted to FDA.
Key Definitions
Prescription Drug Use-Related Software (PDURS): Software distributed by or on behalf of a drug sponsor that generates content supplementing, explaining or otherwise textually related to one or more of the sponsor’s prescription drug products.
End-user output: Content presented by the software to patients, caregivers or healthcare professionals, including screen displays, notifications and audio messages.
Software function: A distinct purpose performed by the software.
Device-connected software function: A software function that relies on data transferred directly from a device or device constituent part of a combination product.
Standalone software function: A software function that does not rely on data transferred directly from a device constituent part, such as a function using information entered by the user.
FDA-Required and Promotional Labeling
FDA recognises two broad categories of prescription drug labeling: FDA-required labeling and promotional labeling. FDA-required labeling includes information reviewed and approved as part of a New Drug Application (NDA), Abbreviated New Drug Application (ANDA), Biologics License Application (BLA), or applicable supplemental application. The Prescribing Information is part of FDA-required labeling and contains essential scientific information needed for the safe and effective use of a drug.
Promotional labeling generally includes other labeling materials disseminated by or on behalf of a drug sponsor. Such materials must be truthful and non-misleading, present balanced information about benefits and risks, and disclose material facts about the drug.
FDA considers PDURS end-user output a type of prescription drug labeling. Its classification depends on factors including whether the software is essential for safe and effective drug use, whether evidence demonstrates a meaningful improvement in clinical outcomes, and whether the software receives data directly from a device constituent part.
When Software Demonstrates a Meaningful Improvement in Clinical Outcomes
Sponsors may provide evidence demonstrating that using PDURS with a prescription drug improves a clinical outcome compared with using the drug without the software. Such evidence should come from one or more adequate and well-controlled studies.
For example, a mobile application used with a diabetes medicine may provide dose reminders, allow users to track blood glucose and weight, and offer behavioural coaching. If FDA determines that the evidence demonstrates a meaningful improvement in glycaemic control, the relevant software information may be included in the Clinical Studies section of the PI.
In these circumstances, the associated end-user output generally constitutes FDA-required labeling. Certain postapproval changes to that output must be reviewed and approved by FDA as applicable to other changes in FDA-required labeling. Sponsors should engage with the relevant FDA review division early when planning clinical studies to support software-related claims.
Device-Connected Software Without Demonstrated Clinical Improvement
Device-connected software may transfer information from a device constituent part to a mobile application without demonstrating a meaningful improvement in clinical outcomes. Examples include an inhaler that records usage or an autoinjector that records the dose and time of administration and transfers the information to an application.
When the software is optional and is not considered necessary for safe and effective drug use, FDA generally recommends a brief description of the device constituent part and associated software function in the How Supplied/Storage and Handling section of the PI. The PI should also indicate that the software is not necessary for the safe and effective use of the product.
In these circumstances, the software-generated end-user output generally constitutes promotional labeling rather than FDA-required labeling.
Standalone Software Functions
Standalone software functions may be described in the PI when they are essential for the safe and effective use of the drug or when adequate and well-controlled studies demonstrate a meaningful improvement in clinical outcomes.
If neither condition applies, the end-user output generally constitutes promotional labeling and the software function generally should not be described in the PI.
Sponsors should therefore evaluate the intended use, clinical evidence and role of each software function before determining how it should be represented in drug labeling.
Submission of Software Output and Updates
End-user output classified as promotional labeling, including applicable updates, must be submitted to FDA using Form FDA 2253 at the time of initial dissemination.
However, software updates that do not change previously submitted end-user output, such as certain security patches or operating system changes, do not require resubmission of that output under the guidance.
FDA may also require a separate device marketing submission when a software function is subject to device regulatory requirements. Form FDA 2253 does not replace the applicable device submission requirements for modifications to an authorised device.
Sponsors developing new or significantly modified device-connected software functions involving a new or modified device constituent part should engage with the appropriate FDA review division.
Regulatory Scope and Applicability
The guidance focuses on how FDA applies drug labeling authorities to software-generated output, regardless of whether the software is regulated as a medical device. It does not change the existing statutory or regulatory framework for medical devices.
Software not distributed by or on behalf of a drug sponsor falls outside the scope of this guidance, even if its developer intends it to be used with a particular prescription drug. Sponsors should also consider whether applicable medical device requirements apply to their software functions.
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