Navigating through regulatory frameworks for digital therapeutics and biomarkers.

Background: Digital health technologies are often subject to regulatory requirements. Regulatory auditing processes are complex but necessary to guarantee quality, efficacy and safety of patients. Evolvements such as digitalized clinical trials, and digital biomarkers require a constant adaption of regulatory frameworks. Objective: This review aims to provide an overview on current regulations and standards for digital therapeutics and digital biomarkers, from technical development to market access. Methods: We conducted an unstructured literature review to identify the relevant guidelines, policies and standards for software based digital therapeutics and digital biomarkers. Results: The principal regulations governing software as a medical device are outlined in Chapter 21 of the Code of Federal Regulations by the US Food and Drug Administration, as well as the European Medical Device Regulation 2017/745. Regulatory pathways, such as the DiGA, are in the process of development, particularly for digital therapeutics, which fall within the purview of software as a medical device. Qualification of (digital) biomarkers is typically voluntary but can play a significant role in the development and approval of digital therapeutics. Conclusions: Fragmented, lacking and diverse regulations around digital biomarkers and digital therapeutics highlight the urge to harmonize and foster regulatory frameworks on an international level.