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Writer's pictureSharan Murugan

USFDA Guidance: Regulatory Considerations for Prescription Drug Use-Related Software

Yesterday (19 September 2023) the U.S. Food and Drug Administration (FDA) released two draft guidance "Regulatory Considerations for Prescription Drug Use-Related Software" and "Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence".


In this guidance, FDA describes how it intends to use its drug labeling authority to approve certain software outputs disseminated by a drug sponsor or on behalf of a drug sponsor.


The FDA recognizes that integrating digital health technologies with prescription drugs holds the potential to create fresh avenues for patient care, and the Agency is actively endeavoring to encourage a responsible, risk-based approach to overseeing digital health in this context. Various software functions, including those associated with mobile applications (apps) are a common example.


The guidance clarifies:

  • How FDA intends to apply its drug labeling authorities to end-user output of prescription drug use-related software

  • How the FDA-required labeling, in particular the Prescribing Information (PI), should describe prescription drug use-related software that:

- Is determined to be essential for the safe and effective use of the drug product, or

- Relies on data directly transferred from the device constituent part of a combination product (see 21 CFR 3.2(e) (defining “combination product”) and 21 53 CFR 4.2 (defining “constituent part”))

  • When and how sponsors should submit end-user output to FDA.


Substantial evidence is defined as evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.


The guidance explains how to determine if an adequate and well-controlled clinical investigation and confirmatory evidence are sufficient to prove substantial efficacy, and gives examples of the types of data that can be considered confirmatory evidence.


Additionally, this guidance emphasizes the importance of early engagement with the Agency for sponsors whose plans include one adequate and well-controlled clinical trial and confirmatory evidence.



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