Regulatory spotlight
DHT Steering Committee
Digital Health Technologies (DHTs) for Drug Development
The central principle of the FDA’s program is that Digital Health Technologies (DHTs) offer significant potential to make clinical trials more efficient, patient-centric, and capable of capturing novel data. A key finding is that a collaborative, multifaceted approach is necessary to address the challenges of incorporating DHT-derived data into regulatory decision-making. The program acknowledges that ensuring data quality, validating new endpoints, and establishing clear regulatory expectations are critical for the successful adoption of these technologies in drug development.
Program Activities (Recommendations)
The FDA’s activities in this area function as implicit recommendations for the industry. The agency is actively:
Developing a Framework: Creating and publishing a clear framework to guide the use of DHTs in drug and biological product development.
Engaging Stakeholders: Convening public meetings and workshops to foster collaboration and share learning among patients, biopharmaceutical companies, DHT manufacturers, and academia.
Supporting Demonstration Projects: Funding and overseeing research projects to address critical gaps and demonstrate the reliability and validity of specific digital measures.
Building Internal Expertise: Establishing a DHT Steering Committee and enhancing internal knowledge to ensure consistent and expert review of submissions containing DHT-derived data.
Regulatory Considerations
This webpage emphasizes the FDA’s commitment to creating a clear regulatory framework for the use of DHTs in drug development. It highlights that while DHTs offer great promise, they also present new regulatory challenges related to data integrity, validation, and analysis. The FDA’s approach involves a combination of issuing new regulatory guidance, promoting stakeholder collaboration, and advancing regulatory science. Sponsors are encouraged to engage with the FDA to discuss their use of DHTs in clinical trials to ensure alignment with the agency’s expectations. The establishment of the CDRH Digital Health Center of Excellence provides a dedicated resource for such engagement.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
The Steering Committee will support the implementation of the framework for the use of DHTs in drug and biological product development as well as other commitments identified in the section “Enhancing Use of Digital Health Technologies to Support Drug Development and Review” of the PDUFA VII commitment letter (e.g., public meetings, guidance documents, demonstration projects, technology needs, training).
In addition, the Steering Committee will oversee activities to assist organizational units with consistent approaches to the review of drug submissions that contain DHT-derived data. Further, the Steering Committee will engage with external interested parties on DHT-related issues in human drug development and gather information about the present state of DHTs, including specific challenges in their use…FDA encourages interested parties who are considering the use of DHTs in drug development or conducting a decentralized clinical trials (DCTs) to reach out to the agency early.
– Digital Health Technologies (DHTs) for Drug Development, FDA, 2024
Q-Submission Program
Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
Pre-Submissions (Pre-Subs) allow submitters to obtain FDA feedback on specific questions before submitting formal IDEs, 510(k)s, PMAs, or other applications. Early feedback can improve submission quality and streamline the review process.
Submission Issue Requests (SIRs) provide a mechanism for addressing issues raised in FDA hold letters (e.g., 510(k) deficiencies) to help expedite resolutions.
Study Risk Determinations help sponsors clarify whether clinical studies are significant risk (SR), non-significant risk (NSR), or exempt from IDE regulations.
Informational Meetings are non-feedback sessions aimed at familiarizing FDA staff with new devices or sharing updates on ongoing development.
The program encourages timely submissions, including supplements for ongoing discussions and amendments to update materials.
Recommendations
Clearly define the purpose and goals of the Q-Sub in the submission to facilitate effective FDA review.
Include specific, well-formulated questions that focus on a limited number of topics to ensure actionable feedback.
For Pre-Subs, align planned testing and submissions with FDA guidance and include detailed device descriptions, testing protocols, and relevant background information.
Use SIRs to discuss proposed solutions to deficiencies raised in FDA hold letters, focusing on timely resolution.
Draft and submit meeting minutes promptly (within 15 days of meetings) to ensure accurate documentation of FDA feedback.
Regulatory Considerations
Submitters should adhere to the timelines specified for different Q-Sub types, including 70 days for Pre-Sub feedback or 21 days for SIRs submitted promptly after a hold letter.
Q-Subs should include all relevant regulatory history and references to prior FDA communications to streamline the review process.
FDA feedback through the Q-Sub program is non-binding and based on the information available at the time; subsequent submissions must align with the provided feedback to maintain consistency.
Informational Meeting requests should clearly state that feedback is not expected and may be used to track interactions outside other formal Q-Sub types.
Confidentiality of Q-Subs is maintained in compliance with FDA’s disclosure regulations and the Freedom of Information Act (FOIA).
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
A Pre-Sub provides the opportunity for a submitter to obtain FDA feedback prior to an intended premarket submission (which, for purposes of this guidance, refers to an IDE, PMA, HDE, De Novo request, 510(k), CW, Dual, Accessory Classification Request, BLA, or IND).
– Section II.A (Pre-Submissions (Pre-Subs)), p. 2, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
The program is entirely voluntary on the part of the submitter. However, early interaction with FDA on planned non-clinical and clinical studies and careful consideration of FDA’s feedback may improve the quality of subsequent submissions, shorten total review times, and facilitate the development process for new devices.
– Section II.A (Pre-Submissions (Pre-Subs)), p. 3, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
FDA has found that feedback is most effective when requested prior to execution of planned testing.
– Section II.A (Pre-Submissions (Pre-Subs)), p. 3, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
To obtain meaningful feedback from FDA, the following should be easily identified within the body of the Q-Sub:
• Purpose
• Device or Product Description
• Proposed Indications for Use or Intended Use
• Regulatory History
– Section III.B(1) (Submission Content), p. 14, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
A Pre-Sub should include clear, specific questions regarding review issues relevant to a planned IDE, IND, CW, Accessory Classification Request, or marketing submission (e.g., questions regarding non-clinical and clinical testing protocols or data needed to support the submission) to allow FDA and the submitter to focus their efforts on issues most relevant to moving a project forward.
– Section III.B(4)(a)1) (Pre-Submission – Additional Recommended Submission Contents: Specific Questions), p. 21–22, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
In general, FDA has found it difficult to address more than 3–4 substantial topics in a single Pre-Sub. … Examples of substantial topics include, but are not limited to, … clinical study endpoints, and statistical analysis plan.
– Section III.B(4)(a)1) (Pre-Submission – Additional Recommended Submission Contents), p. 21–22, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
FDA recommends that sufficient background information and supporting documents be included to allow FDA to develop feedback for the Pre-Sub questions posed. This information might include literature articles, full device description with engineering drawings, proposed labeling, videos, and/or red-lined protocol revisions depending on the specific questions for which feedback is requested. It may also be helpful to include how the submitter addressed, or plans to address, relevant guidance documents, regulations, special controls, or other applicable sources for the specific device or submission type.
While the importance of a complete background package cannot be overstated, it should also be noted that submission of extraneous information can be counterproductive. FDA recommends that a submission be targeted and focused. If significant background information is needed to provide appropriate context, it is helpful if it is indicated which background information is relevant to the specific questions or topics for discussion.
– Section III.B(4)(a)1) (Pre-Submission – Additional Recommended Submission Contents), p. 21, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
A Study Risk Determination is a request for FDA determination for whether a planned medical device clinical investigation is significant risk (SR), nonsignificant risk (NSR), or exempt from most requirements under the IDE regulations (see 21 CFR part 812).
– Section II.C (Study Risk Determinations), p. 4, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
In FDA’s experience, questions that lead to productive Pre-Sub interactions request specific feedback on a limited number of focused topics.
– Appendix 2 (Example Pre-Sub Questions), p. 31, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
Electronic submission template for Q-Submissions
Electronic Submission Template for Medical Device Q-Submissions
This guidance establishes that the eSTAR platform will become the mandatory format for the electronic submission of medical device Pre-Submissions to the FDA. A key principle is that a properly completed eSTAR submission is considered a ‘complete’ submission, which allows it to bypass the traditional Refuse-to-Accept (RTA) process and instead undergo a more focused technical screening within 15 days. The structure of the eSTAR template is designed to align with the FDA’s internal review memo, creating a more efficient and consistent review process. The guidance also makes it clear that while eSTAR use is currently voluntary, it will become required for Pre-Subs at least one year after this guidance is finalized.
Recommendations for Industry
The primary recommendation for industry is to familiarize themselves with and begin voluntarily using the eSTAR platform for Pre-Submissions in advance of the mandatory deadline. The guidance recommends that submitters use the structured, dynamic PDF to ensure all necessary elements of a complete submission are included, thereby facilitating a smoother and more efficient review. For certain types of follow-up communications, such as submitting meeting minutes or presentation slides, the guidance recommends they continue to be submitted as an eCopy rather than through the eSTAR template.
Regulatory Considerations
This guidance is issued under the authority of the Federal Food, Drug, and Cosmetic (FD&C) Act, which mandates the transition to electronic-only submissions. Upon finalization, the requirement to use the eSTAR template for Pre-Subs will be a binding regulatory requirement. The guidance outlines a specific technical screening process for eSTAR submissions that will replace the RTA process. If a submission fails this screening, it will be placed on hold, and the review clock will restart upon receipt of the corrected information. The document also specifies certain types of submissions, such as appeals and withdrawal requests, that will be exempt from the mandatory eSTAR requirement.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
The Food and Drug Administration (FDA or Agency) is issuing this draft guidance document to introduce submitters of Q-Submissions (Q-Subs) to the Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) to the current resources and associated content developed and made publicly available to support certain Q-Sub electronic submissions to FDA, specifically Pre-Submissions (Pre-Subs). This draft guidance is intended to represent one of several steps in meeting FDA’s commitment to the development of electronic submission templates to serve as guided submission preparation tools for industry to improve submission consistency and enhance efficiency in the review process.
– Section I (Introduction), p. 1, Electronic Submission Template for Medical Device Q-Submissions, Draft, 2025 (FDA)
This guidance describes the technical standards associated with preparation of the electronic submission template for Q-Subs that enable submission of the electronic Q-Sub solely in electronic format. Currently, Pre-Subs are the only type of Q-Sub available for electronic submission. This guidance document will be updated accordingly as other Q-Sub types are implemented within the eSTAR program. The electronic submission template includes the information and guided prompts FDA believes will best facilitate the collection and assembly of the necessary elements of a ‘complete’ submission. This guidance is not intended to specify the user-interface and detailed content of the eSTAR, but instead is limited to establishing the Q-Sub electronic format and standards for complying with section 745(A)(b)(3) of the FD&C Act. FDA intends to implement new versions of eSTAR as relevant policies change. FDA also has an ongoing process to collect and consider public comments and stakeholder feedback, which is described on FDA’s website.
– Section III (Scope), p. 4, Electronic Submission Template for Medical Device Q-Submissions, Draft, 2025 (FDA)
Formal meetings related to PDUFA products
Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry
The guidance establishes a predictable and efficient framework for formal interactions between the FDA and sponsors. Its core principle is that timely, high-quality communication is critical to a streamlined drug development process. The document clarifies that different stages of development require different types of meetings (e.g., Type A, B, and C), each with specific timelines and objectives. A key principle is that productive meetings depend on the sponsor providing a comprehensive meeting package in advance, allowing the FDA to prepare and provide substantive feedback.
Recommendations for Sponsors
Sponsors are strongly recommended to engage with the FDA early and throughout the drug development process. To ensure a productive meeting, sponsors should clearly articulate the purpose of the meeting, provide specific questions, and submit a well-organized and complete meeting package by the specified deadline. It is recommended that sponsors carefully consider the type of meeting that is most appropriate for their stage of development and the nature of the questions they have. Following the meeting, sponsors should adhere to the timelines and procedures for submitting meeting minutes for the official record.
Regulatory Considerations
This guidance is a key component of the regulatory framework under the Prescription Drug User Fee Act (PDUFA). Adherence to the procedures outlined in this document is a matter of regulatory compliance. The formal meetings described are a critical part of the Investigational New Drug (IND) and Marketing Authorization Application processes. The meeting process is designed to provide regulatory clarity, reduce the risk of clinical holds or refuse-to-file actions, and ultimately support a more efficient and predictable path to drug approval. The written record of these meetings serves as an important part of the administrative file for a product’s development program.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Premeeting preparation is critical for achieving a productive discussion or exchange of information. Preparing the meeting package should help the requester focus on describing its principal areas of interest. The meeting package should provide information relevant to the discussion topics and enable the FDA to prepare adequately for the meeting.
– Section VII (Meeting Package), p. 14, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, September 2023 (FDA)
Remote Data Acquisition
Digital Health Technologies for Remote Data Acquisition in Clinical Investigations
There is a need for comprehensive validation and verification processes for DHTs.
Ensuring data security and privacy is a significant concern.
Usability issues for diverse populations need to be addressed.
There is a lack of clarity on whether certain DHTs meet the definition of a device under the FD&C Act.
The guidance does not establish legally enforceable responsibilities.
Recommendations
Ensure DHTs are fit-for-purpose for clinical investigations.
Implement robust data security measures to protect participant information.
Conduct usability evaluations to ensure DHTs can be used by intended populations.
Engage with FDA early to discuss the use of DHTs in clinical investigations.
Develop a risk management plan to address potential issues with DHT use.
Regulatory Considerations
Verification and validation should be addressed regardless of device classification.
Sponsors should ensure compliance with data protection and privacy regulations.
FDA evaluates DHT data based on endpoints, medical products, and patient populations. Sponsors can engage with FDA’s Q-Submission Program for feedback on DHT usage in clinical trials.
Sponsors should understand the legal implications of using DHTs in clinical investigations.
The guidance provides recommendations but does not establish legally enforceable responsibilities.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Some DHTs that may be appropriate for use in a clinical investigation may meet the definition of a device under section 201(h) of the FD&C Act. Devices intended for use in clinical investigations, including DHTs, are exempt from most regulatory requirements applicable to devices, including marketing authorization, as long as the investigation complies with applicable requirements under 21 CFR part 812.
– Section III (Regulatory Considerations and Engagement with the Agency), p. 6, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
In many cases, FDA regulations do not require submission of an IDE application to FDA for use of a device in a clinical investigation. For example, where a DHT, as proposed for use in a clinical investigation of a drug or biological product under an IND, is a nonsignificant risk device (i.e., the DHT does not meet the definition of a significant risk device under 21 CFR 812.3(m)), submission of an IDE application to FDA is not required if the investigation complies with the abbreviated requirements in 21 CFR 812.2(b).
– Section III (Regulatory Considerations and Engagement with the Agency), p. 6, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA).
In submissions that rely on or propose a clinical investigation that includes the use of a DHT, the sponsor should explain how the DHT is fit-for-purpose for use in the clinical investigation. The description should include information such as design and related technological characteristics of the DHT, data output provided to the sponsor and investigator, and information on how the DHT measures the clinical event or characteristic of interest.
– Section IV.B (Digital Health Technology Description in a Submission), p. 10–11, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA).
When the sDHT is a regulated medical device: Cybersecurity in medical devices
Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions
Cybersecurity threats in healthcare are increasingly frequent and severe, posing risks to device safety and clinical care.
Many vulnerabilities arise from third-party software components and interconnected device ecosystems.
Legacy devices often lack adequate cybersecurity controls, leading to increased patient and organizational risks.
Cybersecurity risk management processes must integrate safety and security assessments throughout the device lifecycle.
Transparency in device cybersecurity is crucial for enabling safe integration and use by healthcare providers and end users.
Recommendations
Implement a Secure Product Development Framework (SPDF) for comprehensive cybersecurity throughout the product lifecycle.
Include a Software Bill of Materials (SBOM) for all premarket submissions to track software dependencies and vulnerabilities.
Perform robust cybersecurity testing, including penetration testing and vulnerability assessments.
Enhance device labeling with clear cybersecurity-related instructions and risks for users.
Develop a coordinated vulnerability disclosure plan for postmarket cybersecurity management.
Regulatory Considerations
Adherence to 21 CFR Part 820 Quality System regulation requirements, including design controls and risk management.
Compliance with Section 524B of the FD&C Act for cybersecurity of cyber devices.
Submission of SBOMs and detailed security risk management reports for premarket applications.
Provision of cybersecurity information as part of device labeling to prevent misbranding under Section 502 of the FD&C Act.
Integration of security testing and validation as part of the FDA review process.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
FDA understands the need to balance innovation and security in designs especially during clinical trials. In order to ensure security is addressed early in the device design, FDA has identified a subset of the documentation recommended throughout this guidance to submit with IDE applications. Under 21 CFR 812.25, manufacturers must provide an investigational plan as a part of their IDE application. For investigational devices within the scope of this guidance, FDA recommends that this investigational plan include information on the cybersecurity of the subject device. Specifically, FDA recommends the following documentation be included as part of IDE applications:
- Inclusion of cybersecurity risks as part of informed consent form (21 CFR 50.25(a)(2) and 21 CFR 812.25(g));
- Global, multi-patient and updateability/patchability views (21 CFR 812.25(c), (d));
- Security use case views for functionality with safety risks (e.g., implant programming) (21 CFR 812.25(c), (d));
- Software Bill of Materials (21 CFR 812.25(c), (d)); and
- General labeling – connectivity and associated general cybersecurity risks, updateability/process (21 CFR 812.25(f)).
– Appendix 3 (Submission Documentation for Investigational Device Exemptions), pp. 50, Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions, Final, 2025 (FDA)
Critical Path Innovation Meetings (CPIM)
Critical Path Innovation Meetings (CPIM)
The core principle of the Critical Path Innovation Meeting (CPIM) program is that early, non-binding communication between the FDA and innovators can accelerate the development of new Drug Development Tools (DDTs). The program is designed to be a collaborative, scientific discussion, not a formal regulatory review of a specific product. A key finding from the program’s existence is that a dedicated forum to discuss emerging science—outside the context of a specific drug application—is critical for advancing regulatory science and modernizing the drug development process.
Recommendations for Stakeholders
The program implicitly recommends that innovators (from industry, academia, etc.) proactively seek the FDA’s perspective on novel methodologies and technologies. Stakeholders are encouraged to request a CPIM to discuss potential biomarkers, novel clinical outcome assessments (COAs), innovative clinical trial designs, and other new tools. The goal is for sponsors to gain a better understanding of the FDA’s thinking on a particular topic, which can help guide their development efforts and de-risk future regulatory submissions.
Regulatory Considerations
A CPIM is an informal, non-binding scientific discussion and does not replace formal regulatory meetings like pre-IND or End-of-Phase meetings. The advice provided by the FDA during a CPIM does not constitute a regulatory decision or a commitment for a future approval pathway. The program is part of the FDA’s broader “Critical Path Initiative” and is intended to promote innovation by enhancing communication. Any outcomes or suggestions from a CPIM are for informational purposes to help guide the development of novel tools and approaches.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
The goals of the CPIM are to discuss a methodology or technology proposed by the meeting requester and for CDER to provide general advice on how this methodology or technology might enhance drug development. CDER will identify some of the larger gaps in existing knowledge that requesters might consider addressing during their work. CDER expects to become more familiar with prospective innovations in drug development, broadening its regulatory perspective. CPIM discussions are non-regulatory, drug product-independent and nonbinding on both FDA and CPIM requesters.
– Critical Path Innovation Meetings (CPIM), FDA, 2022- Critical Path Innovation Meetings (CPIM), FDA, 2022
Once you’ve read the guidances, explore these best practices from the field:
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