As we kick off 2022, several recent developments from FDA suggest that this year could be pivotal for the Agency’s digital health priorities.  From new FDA offices and artificial intelligence guidance, to FDA’s user fee commitments and must-pass legislation in Congress, this post outlines five key issues to watch in 2022 related to FDA and digital health.  For all of these issues, stakeholders should be mindful of areas where digital health can help address some of the health disparities highlighted by the pandemic (e.g., ability to reach more clinical trial participants using wearables and other technologies, use of real-world evidence to better understand treatment effects in underrepresented populations, at-home software and diagnostic solutions).

1.         FDA’s Digital Transformation

Significant work continues within the Agency to advance digital health priorities, including both organizational and regulatory policy changes.

As an organization, FDA continues to evolve in an effort to keep pace with trends in digital health and data analytics.  For example, on September 15, 2021, FDA announced a new Office of Digital Transformation (ODT), which is tasked with advancing FDA’s overarching technology and data modernization efforts.  ODT sits in the FDA Office of the Commissioner and encompasses the Agency’s information technology, data management, and cybersecurity functions.  The formation of ODT follows two years of modernization efforts, including the 2019 Technology Modernization Action Plan and the 2021 Data Modernization Action Plan.  FDA recently named Vid Desai as the Director of ODT, and the Agency’s FY 2022 budget request included funding to support these data modernization efforts, further demonstrating the commitment to these institutional changes.  At the center level, FDA’s Center for Devices and Radiological Health (CDRH) launched the Digital Health Center of Excellence (DHCoE) in 2020 to help coordinate digital health projects at CDRH and enhance coordination with other agency centers.  On the data analytics front, the Real-World Evidence (RWE) Subcommittee composed of CDER and CBER officials continues to advance the use of real-world data/evidence (RWD/E) in agency decision making, and in early January 2022, FDA highlighted proposed changes to CBER’s Office of Biostatistics and Epidemiology aimed at positioning CBER to “advance real-world evidence priorities for biologics,” noting that “harnessing the power of real-world evidence” is a priority for the Agency.

On the regulatory policy front, FDA continues to issue new policies.  For example, on December 22, 2021, CBER, CDER, and CDRH issued a draft guidance on the use of “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations,” which addresses the use of computing platforms, software, and sensors to facilitate remote data acquisition during clinical investigations.  CDRH’s FY 2022 agenda prioritizes other software-related guidance documents, including final guidance on Clinical Decision Support (CDS) Software and draft guidances on risk categorizations for Software as a Medical Device (SaMD) and the content of premarket submissions for SaMD (which FDA published early in FY 2022, on November 4, 2021).  It also is possible that FDA will apply some of the lessons from FDA’s Pre-Cert Pilot Program to develop new approaches for software developers.  Drug sponsors continue to watch what (if anything) FDA will do with the proposed November 2018 PDURS Framework regarding “prescription drug-use-related software.”  In sum, expect an active FDA in 2022.

2.        AI/ML-Based Software Regulation

FDA recognizes the potential for AI/ML-based software to transform healthcare and has outlined several priorities regarding AI/ML-based software as a medical device (AI/ML-based SaMD).  In a January 2021 AI/ML-Based SaMD Action Plan, FDA recognized that adaptive AI/ML-based SaMD raise unique regulatory issues, such as how to manage device modifications after FDA clearance, and how to determine which modifications trigger the need for FDA premarket review.  FDA has proposed a regulatory framework to potentially allow for modifications to algorithms based on real-world, postmarket learning and adaptations while maintaining safety and effectiveness.  The 2021 Action Plan addressed stakeholder feedback on an earlier discussion paper, and promised to update the proposed framework for AI/ML-based SaMD, including through issuance of draft guidance.  CDRH’s FY 2022 agenda included a proposed guidance document for premarket submissions that outlined a change control plan for AI/ML-based SaMD.  To provide greater transparency, CDRH also launched an Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Device List.  The list—though not exhaustive—contains publicly available information on AI/ML-enabled devices marketed in the U.S., many of which currently have “locked” algorithms (i.e., algorithms that do not change without human intervention).

On the global stage, FDA, Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) identified 10 guiding principles that can inform the development of Good Machine Learning Practice (GMLP) in an October 2021 guidance titled, “Good Machine Learning Practice for Medical Device Development: Guiding Principles.”  The guiding principles aim to promote safe, effective, and high-quality AI/ML-based medical devices.  For more information on these principles, see our previous post here.  Also, the International Medical Device Regulators Forum (IMDRF) AI Working Group released a draft guidance on September 16, 2021, titled “Machine Learning Enabled Medical Devices – a Subset of Artificial Intelligence: Key Terms and Definitions.” This guidance aims to establish relevant terms and definitions across the total product lifecycle to promote consistency and support global harmonization efforts.  Bottom line, watch for continued emphasis in 2022 on developing the appropriate regulatory framework for AI/ML-based SaMD.

3.        PDUFA & MDUFA Reauthorization in Congress

Digital health priorities are embedded in the Agency’s user fee commitments for fiscal years (FYs) 2023 through 2027.  As background, the Prescription Drug User Fee Act (most recently reauthorized as PDUFA VI) and the Medical Device User Fee Act (most recently reauthorized as MDUFA IV) sunset every five years, unless reauthorized by Congress, and PDUFA VI and MDUFA IV expire on September 30, 2022.  The reauthorization of PDUFA and MDUFA is regarded as “must-pass” legislation in Congress, given the critical nature of user fees to FDA’s activities.

As part of the reauthorization process, FDA has negotiated user fee commitment letters with the relevant regulated industries, taking input from patient and consumer groups along the way.  These commitment letters outline the performance goals agreed to by the Agency for the next five fiscal years, if Congress reauthorizes the associated user fee levels.

In its PDUFA VII commitment letter, published August 23, 2021, FDA committed to expanding the role of digital health technologies in drug development, drug reviews, and decentralized clinical trials.  Between FYs 2023 through 2027, FDA commits to establish a digital health technology framework, identify demonstration projects to inform evaluations of digital health technologies, issue guidance on the use of digital health technologies in clinical trials, and expand its digital health staff and expertise.  FDA also plans to host public meetings to gather input on issues related to use of digital health technologies in regulatory decision making.  As further discussed under Issue 5, FDA also committed to take steps to advance the use of RWD/E.

FDA has yet to publish the MDUFA V commitment letter, but meeting minutes from industry and stakeholder discussions suggest that digital health is a topic of interest.  Industry should watch for the MDUFA V commitment letter and then monitor whether Congress adds additional legislative changes on digital health topics for both drugs and devices as part of the 2022 user fee reauthorization.

4.        Software-Related Policies in Cures 2.0 and the VALID Act

Two key bills being considered in Congress include provisions that would impact FDA’s digital health policies: the VALID Act and Cures 2.0.

First, on June 24, 2021, Sens. Michael Bennet (D-CO) and Richard Burr (R-NC) and Reps. Diana DeGette (D-CO) and Larry Buschon (R-IN) reintroduced a revised version of the Verifying Accurate Leading-edge IVCT Development (VALID) Act, following up on its initial introduction in March 2020.  The VALID Act’s definition of “in vitro clinical test” currently encompasses software used in diagnostic testing.  If enacted, this could result in software used in connection with diagnostic tests being regulated under the new VALID Act framework.  Stakeholders should monitor the legislation and, if it is enacted, how that new framework would intersect with FDA’s other digital health policies, such as those relating to CDS software.

Second, Congressional leaders Diana DeGette (D-DO) and Fred Upton (R-MI) are working on a bipartisan follow-up to the 2016 21st Century Cures Act, deemed “Cures 2.0.”  As discussed in a previous post, Cures 2.0 was introduced in the House on November 17, 2021 and lays out several notable policies related to digital health, RWD/E, and telehealth, among other provisions.

Stakeholders should monitor how these legislative proposals advance in Congress this year, including as potential amendments to the “must-pass” FDA user fee reauthorization discussed in Issue 3.

5.        FDA’s Real-World Evidence (RWE) Program

FDA continues to advance the use of RWD/E as part of the agency’s regulatory decision making.  As background, CDER and CBER published a framework in 2018 for FDA’s RWE Program for human drugs and biological products, as required by section 3022 of the 21st Century Cures Act.  The Cures Act also required FDA to issue guidance documents by December 13, 2021, regarding the circumstances under which drug sponsors may rely on RWD/E and the appropriate standards and methodologies for the collection and analysis of RWD/E.  In line with this requirement, FDA recently published four significant draft guidance documents:

1. RWD: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products (September 2021)
2. Data Standards for Drug and Biological Product Submissions Containing RWD (October 2021)
3. Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products (November 2021)
4. Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products (December 2021)

CDRH has been active in this space as well, issuing a guidance in 2017 on the use of RWD/E to support regulatory decision-making for medical devices and issuing a report last year outlining examples of RWD/E used in various regulatory decisions involving devices.

As stated in FDA’s PDUFA VII commitment letter (and as previewed under Issue 3), FDA intends to launch a pilot “Advancing Real-World Evidence (RWE) Program” with three key goals: (1) to identify approaches for generating RWE that meet regulatory requirements; (2) to develop agency processes that promote consistent decision-making and shared learning regarding RWE; and (3) to promote awareness of characteristics of RWE that can support regulatory decisions by allowing FDA to discuss study designs considered in the Advancing RWE Program in a public forum.  As part of this Pilot, sponsors can apply to participate in the Advancing RWE Program meetings, which will provide an optional pathway for submitting RWE proposals.  Sponsors who do not participate in the pilot program will still have an opportunity to engage with the Agency on RWE issues through existing channels.  In its PDUFA VII commitment letter, FDA also commits to reporting out information regarding RWE submissions to CDER and CBER by June 2024 and updating RWE guidance (or drafting new guidance) reflecting FDA’s experience with the Pilot Program by December 2026.

Bottom line, watch for additional FDA decisions and actions on the RWD/E front in 2022, including as the Agency prepares for its 2023 PDUFA VII commitments.