3.1 Preparing for effective regulator engagement

OVERVIEW

Foundations for regulatory discussions

Effective regulatory engagement begins with internal preparation. This foundational work can lead to stronger conversations with FDA, reducing the risk of fragmented feedback and improving the likelihood of favorable outcomes.

This step also ensures your sDHT strategy connects to the broader work you’ve done in earlier sections of the Roadmap: the patient-informed endpoints from Section 2.1: Patient-informed endpoints, the [context of use (COU)] or [intended use] you defined in Section 2.2: Context of use, and the stakeholder alignment you built in Section 2.3: Stakeholder alignment. Regulatory engagement is where that preparation meets external review.

The landscape of FDA engagement options

FDA offers multiple mechanisms for engaging with sponsors and developers at different stages of product development. These mechanisms are established under user fee programs—MDUFA (Medical Device User Fee Amendments) for devices, and PDUFA (Prescription Drug User Fee Act) for drugs and biologics, which set performance goals for FDA review timelines and meeting scheduling.

Before diving into the specifics of which pathway fits your situation (Section 3.2: Pathway selection and timing), it helps to understand the landscape.

Which engagement mechanism should I start with?

Many sDHT regulatory questions fall into one of four starting points:

Using an sDHT in a medical device trial, or the sDHT itself is a device

[Q-Submission (Q-Sub)] to [CDRH]

Using an sDHT in a drug or biologic trial with an active or planned IND

DHT Steering Committee email, then [PDUFA meeting]

Exploring a novel methodology not yet tied to a specific product

DHT Steering Committee email to determine appropriate path

Seeking formal qualification for broad reuse across programs

See Section 3.3: Formal qualification programs for [MDDT] or [DDT] qualification pathways

The information below provides an overview of some of the primary engagement mechanisms relevant to sDHT development. Note that some pathways are specific to drug/biologic development (administered by [CDER] or [CBER]), while others are specific to medical device development (administered by [CDRH]). A few mechanisms support cross-center coordination.

Each serves different purposes and carries different levels of formality. Informal mechanisms (like email inquiries or DHT Steering Committee outreach) are useful for early orientation and routing questions. Formal mechanisms (like Q-Submissions and PDUFA meetings) generate documented feedback that shapes your development program. Section 3.2: Pathway selection and timing provides additional insights based on whether your sDHT is being used in a medical device trial or a drug/biologic trial. DDT and MDDT formal qualification programs, covered in Section 3.3: Formal qualification programs, are pathways for tools intended for broad reuse across multiple programs.

Examples of early touchpoint opportunities

Once your objectives are clear and teams aligned, consider these early touchpoints for initial FDA outreach—detailed further in Section 3.2: Navigating regulatory pathways.

Email a help desk DHT Steering Committee PDUFA INTERACT Q-Sub Breakthrough Devices

Email a front-door help desk; these teams can route early questions and point you to the right program or review division.

Drugs/biologics:

• DHT Steering Committee — DHTsforDrugDevelopment@fda.hhs.gov

Medical devices (including sDHTs that qualify as medical devices):

• Digital Health Center of Excellence (DHCoE) — digitalhealth@fda.hhs.gov

Primary context: Drug/biologic trial

DHT Steering Committee Outreach

Reach out via email (DHTsforDrugDevelopment@fda.hhs.gov) for initial questions about using sDHTs.

Best for
This is an option for informal feedback and for questions not tied to a specific trial.
Applicable FDA Center(s)
Cross-center (CDER, CBER, CDRH coordination)

Feedback type
Email inquiry; response time varies

Primary context: Drug/biologic trial

PDUFA Meetings (Types A, B, C, D)

For sponsors with an active or planned [IND] seeking formal FDA feedback at development milestones.

Device sponsors may use PDUFA meetings when the sDHT is part of a combination product with a drug component.

Best for
Formal milestones and key decision points in drug development. Type A for urgent issues, Type B for phase transitions, Type C for other topics not aligned to Type A or B; and Type D for narrowly focused issues, which can be particularly useful for targeted sDHT questions that arise during a trial.

Applicable FDA Center(s)
CDER/CBER (primary; CDRH for device elements in combinations; can request DHCoE or Patient Science expertise if relevant).

Timing & format
Correspond to milestones and decision points; 30-75 days turnaround.

Feedback type
FDA provides meeting discussion with minutes.

Primary context: Drug or Biologic trial

INTERACT Meeting

For early, informal feedback on complex biologics or innovative products before a pre-IND submission—particularly when facing novel challenges related to product characterization, manufacturing, or IND-enabling studies. Limited applicability to devices; use Q-Sub for device-specific questions.

Best for
Early, informal advice for complex biologics or innovative products, focusing on preliminary issues like product characterization.

Applicable FDA Center(s)
CDER/CBER (can request DHCoE or Patient Science expertise if relevant).

Timing & format
Pre-IND.

Feedback type
FDA provides informal discussion.

Primary context: Medical device trial

Q-Submissions come in several types including Pre-Submission (Pre-Sub) for feedback from FDA to help guide product development; Informational meetings; Study Risk Determinations; and Submission Issue meetings. Q-subs are for sDHTs meeting the definition of a medical device, not all sDHTs qualify.

Ideal for sDHTs that qualify as medical devices or are being used as measurement tools in device development trials.

Drug/biologic sponsors may encounter Q-Subs when the sDHT evaluating an endpoint in a drug trial is a regulated device (e.g., in combination products). In these cases, the device component would be reviewed through CDRH’s Q-Sub process in coordination with CDER/CBER.

Best for:
Pre-submission feedback on technical, validation, or submission plans. Ideal for sDHTs that qualify as medical devices (standalone or marketed) or in device-related trials, including Pre-Subs for iterative advice.

Applicable FDA Center(s)
CDRH (primary for devices; coordinates with CDER/CBER for combinations; involves treatment area reviewers like lead/clinical; can request Digital Health Center of Excellence (DHCoE) or Patient Science expertise if relevant).

Timing & format
Early to mid-development; written response or meeting within 45-90 days.

Feedback type
FDA provides written feedback or meeting discussion.

Primary context: Medical device trial

Breakthrough Devices Program

For sDHTs that qualify as medical devices and offer significant advantages over existing alternatives for life-threatening or irreversibly debilitating conditions. Provides expedited review, interactive communication, and senior FDA involvement. Not applicable to drugs or biologics—use Breakthrough Therapy Designation for those products.

Best for
Expedited review for innovative devices with significant advantages over existing options, including “sprint” discussions for rapid feedback.

Applicable FDA Center(s)
CDRH (can request DHCoE or Patient Science expertise if relevant).

Timing & format
Post-concept; includes prioritized review and interactive communication.

Feedback type
FDA provides interactive communication.

MDUFA and PDUFA are the legislative frameworks that fund and structure FDA’s engagement mechanisms. MDUFA (Medical Device User Fee Amendments): Establishes Q-Submission program, performance goals for device reviews, and pre-market consultation timelines. Similar to PDUFA meetings, MDUFA supports formal consultations with CDRH throughout device development. PDUFA (Prescription Drug User Fee Act): Establishes meeting types (A, B, C, D, INTERACT), response timelines, and formal meeting structure for drug and biologic sponsors.

While the legislative names differ, the underlying principle is the same: providing structured engagement opportunities at critical development milestones. Throughout this Roadmap, we refer to “Q-Submissions” (device context) and “PDUFA meetings” (drug/biologic context) as primary formal engagement mechanisms under these respective programs.

Cross-functional alignment: building internal consensus

Before initiating FDA engagement, confirm that your internal teams are aligned on the scientific, operational, and regulatory strategy for incorporating an sDHT into your clinical research. Use the checklist below to identify gaps. Not every item will apply to every situation—focus on the categories most relevant to your current development stage.

Cross-functional alignment checklist

This checklist builds directly on the stakeholder work from Section 2.3: Stakeholder alignment. Where that section focused on aligning around endpoint selection and patient relevance, this checklist ensures that alignment carries forward into your regulatory engagement strategy.

How to use this checklist:

Adopters
Use this checklist to guide a 30–45 minute internal “pre-engagement alignment” meeting. Invite clinical, regulatory, endpoint/clinical outcome specialists, data scientist, and digital strategy leads.

Developers
Adapt this checklist as a readiness tool to organize your evidence and prepare for partnership discussions or independent regulatory outreach.

Endpoint alignment Internal alignment Operational preparedness Regulatory engagement

Is the selected digital measure traceable to a patient-prioritized meaningful aspect of health identified in Section 2.1: Patient-informed endpoints

Has the endpoint concept of interest been clearly articulated and agreed upon?

Are internal stakeholders aligned on the specified context of use, including patient population, trial setting, and endpoint type (e.g., exploratory, secondary, primary)?

Have prior external stakeholder insights (e.g., patient advocacy groups, Delphi panels, COA specialists) been documented and translated into regulatory-relevant framing?

PRO TIP FOR DEVELOPERS

Even without a specific therapeutic indication or adopter partner, articulating how your measure connects to a meaningful aspect of health will strengthen any regulatory submission and demonstrate value to future partners.

Have digital health leads, COA specialists, clinical scientists, and regulatory affairs reviewed the endpoint strategy together?

Is there consensus on how the sDHT will support the selected digital endpoints?

Have internal discussions resolved whether the digital measurement is best positioned as a biomarker or a clinical outcome assessment (COA)—and are implications for FDA engagement understood?

Have data science or statistical teams reviewed the sDHT’s anticipated output, format, and reliability, and developed a high-level plan for how the data could be analyzed and incorporated into a statistical analysis plan?

Have privacy, legal, or compliance leads reviewed any implications of data flow or monitoring responsibilities?

PRO TIP FOR DEVELOPERS

Adopters draft the statistical analysis plan (SAP), but you play a critical role by providing data specifications, performance evidence, and examples of feasible analyses. Showing how sDHT outputs translate into analyzable endpoints helps align teams early and avoids surprises later.

Has the V3+ status of the sDHT been summarized and circulated internally (see Section 4: Your validation strategy)?

Is there an agreed approach to address data integrity, missing data, and patient adherence in trial implementation?

Have stakeholders agreed on data access and ownership boundaries (e.g., raw vs. derived data, access by adopter vs. developer)?

Is there an executed confidentiality agreement that allows for shared regulatory engagement?

PRO TIP FOR DEVELOPERS

Maintain a concise, up-to-date summary of your V3+ status (see Section 4: Your validation strategy). Include completed and in-progress validation efforts so adopters and regulators can quickly assess your technology’s readiness.

Is there agreement on which FDA engagement type is appropriate at this stage (e.g., DHT Steering Committee, Q-Sub, PDUFA)?

If this is not the first engagement, ave prior FDA interactions (e.g., meeting minutes, earlier Pre-Subs) been located and reviewed?

Has a draft briefing document or concept sheet been reviewed across functions to ensure alignment on key messages and evidence gaps?

Are internal timelines aligned with expected FDA review timelines (e.g., 60–75 days for Q-Sub, 30–60 days for PDUFA meeting)?

Have all internal stakeholders been invited to participate in pre-engagement prep meetings, including mock discussions if needed?

PRO TIP FOR DEVELOPERS

Pre-Submissions (Q-Subs) and other early engagements are open to developers without an IND. These interactions can shape your validation roadmap and demonstrate to future adopters that you’ve proactively engaged regulators.

key takeaways

Effective regulator engagement begins before you contact FDA.

1. Define your objective clearly.
Know what feedback you need, what decision it will inform, and what evidence you can provide.

2. Align internally first.
Cross-functional consensus prevents fragmented messaging and ensures your briefing materials tell a coherent story.

3. Understand the landscape.
Multiple engagement mechanisms exist for different purposes and development stages. The right choice depends on your specific context—which Section 3.2: Navigating regulatory pathways addresses in detail.

4. Start with a sanity check when uncertain.
Early, informal interactions can clarify whether you’re on the right track before you invest in formal submissions.