Regulatory spotlight
MDDT qualification
Qualification of Medical Device Development Tools
Lack of publicly available qualified MDDTs may limit their widespread adoption.
Challenges in collecting robust evidence for novel or innovative tools without established paradigms.
Regulatory complexities for tools with dual uses as MDDTs and clinical diagnostic devices.
The need for transparent communication of MDDT advantages and limitations for their qualified COU.
Limited industry awareness of the benefits and processes for MDDT qualification.
Recommendations
Develop clear and specific Context of Use (COU) statements for proposed MDDTs, detailing their application in device evaluation.
Ensure thorough validation of tool performance characteristics, including accuracy, reproducibility, and reliability, to support qualification.
Foster collaboration among stakeholders, such as consortia and organizations, to share resources for MDDT development and qualification.
Provide detailed qualification plans outlining data collection methods, protocols, and acceptance criteria for each performance metric.
Promote transparency by publishing high-level summaries of evidence and qualification decisions while protecting proprietary information.
Regulatory Considerations
MDDTs intended only for device evaluation are typically not classified as medical devices unless used for clinical treatment or diagnosis.
Clinical study tools used as MDDTs must comply with Investigational Device Exemption (IDE) regulations under 21 CFR Part 812.
Qualification does not imply FDA clearance or approval for clinical use; labeling and promotional materials must clearly communicate this distinction.
Modifications to an MDDT’s COU or qualification status may require reevaluation based on new data or scientific advancements.
FDA emphasizes the complementary role of MDDTs alongside consensus standards and device-specific guidance for regulatory evaluations.
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.
Medical Device Development Tool (MDDT) is a method, material, or measurement used to assess the safety, effectiveness, or performance of a medical device.
Qualification is a conclusion based upon FDA review of the MDDT Qualification Package. A qualification decision signifies that the MDDT can be relied upon to facilitate regulatory decision making when it is used according to the qualified COU.
– Section II (Definition of Key Concepts), p. 2, Qualification of Medical Device Development Tools, July 17, 2023 (FDA)
The intent of this voluntary CDRH MDDT program is to promote the development and use of MDDTs to streamline device development and regulatory evaluation. Once an MDDT is qualified for a specific COU, CDRH encourages MDDT developers to make their qualified MDDT(s) publicly available, which can include under a licensing arrangement, so that the MDDT(s) can be used by any medical device manufacturer for the qualified COU. CDRH reviewers should accept the MDDT for the qualified COU without the need to reconfirm the suitability and utility of the MDDT when used in a CDRH regulatory submission. CDRH review divisions maintain the responsibility for evaluating regulatory submissions using the totality of evidence in addition to the information obtained from a qualified MDDT.
– Section III.A (What is an MDDT & MDDT qualification?), p. 4, Qualification of Medical Device Development Tools, July 17, 2023 (FDA)
The MDDT program is a way for the FDA to qualify tools that medical device sponsors can choose to use in the development and evaluation of medical devices. Tools such as biomarker tests, clinician-reported outcome measures, patient-reported outcome measures, or non-clinical assessment models such as animal or computational models, and digital health technologies like sensors or wearables, play an important role in helping the FDA understand how medical devices work, in terms of safety, effectiveness, and other aspects of performance.
MDDT qualification is a conclusion that within the stated context of use, the results of an assessment that uses an MDDT can be relied upon in device evaluation and to support regulatory decision-making.
– Medical Device Development Tools, FDA, 2024
MDDT example
Medical Device Development Tool (MDDT) Summary of Evidence and Basis of Qualification – Apple Atrial Fibrillation History Feature
Clinically Acceptable Performance: A clinical study demonstrated that the weekly AFib burden estimates from the Apple AFib History Feature were in close agreement with a reference ECG patch, with an average difference of just 0.67%. The vast majority of measurements had paired differences within ±10% of the reference device.
Generalizable Across Subgroups: The device’s accuracy was similar across various subgroups, including different sexes, races, ages, and skin tones.
Performance Post-Ablation is Uncertain: In a small subgroup of patients with a prior cardiac ablation, the device’s performance, while still strong, showed slightly more variability and exceeded a pre-specified acceptance criterion. The study was not designed or powered to demonstrate equivalent performance in this specific group.
Technical Limitations Exist: The feature only provides a retrospective weekly estimate and does not give specific timestamps or durations of AFib episodes. It also does not detect other atrial tachyarrhythmias, like atrial flutter.
Recommendations
Appropriate Use: The document implicitly recommends using the tool precisely within its qualified context of use—as a secondary, not primary, endpoint for comparing AFib burden between study arms in cardiac ablation device trials.
Supplemental Data Collection: For studies involving patients who have had a prior ablation, it would be beneficial to assess the tool alongside other methods of determining AFib burden to better characterize its performance in this population.
Define Study-Specific Endpoints: Investigators using the tool are responsible for defining and justifying their specific study designs and what constitutes a clinically significant reduction in AFib burden.
Regulatory Considerations
MDDT Qualification: The Apple AFib History Feature is officially qualified by the FDA as a Medical Device Development Tool (MDDT), which reduces the burden on device developers, as they no longer need to independently justify its methodology for collecting weekly AFib burden estimates in their clinical studies.
Secondary Endpoint Only: A key limitation for its regulatory use is its qualification only as a secondary endpoint. It cannot, by itself, be used to evaluate the primary safety and effectiveness of cardiac ablation devices. This is partly because FDA typically requires the inclusion of any atrial tachyarrhythmia (not just AFib) for defining ablation success in pivotal studies.
Not a Replacement for Primary Endpoints: The tool’s utility is intended to provide supplemental data and help better understand post-treatment AFib burden; it is not meant to replace more clinically well-defined primary endpoints.
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’s official Summary of Evidence and Basis of Qualification for the Apple Atrial Fibrillation History Feature as a Medical Device Development Tool (MDDT).
– Medical Device Development Tool (MDDT) Summary of Evidence and Basis of Qualification, December 21, 2023
DDT qualification
Drug Development Tool (DDT) Qualification Programs
The central principle of the DDT Qualification Programs is to create a formal pathway for the FDA to conclude that a specific tool is well-suited for a particular Context of Use (COU) in drug development. A key finding, as reflected in the program’s design, is that qualification de-risks drug development by allowing a tool to be used in any regulatory submission for its qualified COU without needing to be re-validated each time. The program is designed to foster stakeholder collaboration, encouraging the development of tools that can benefit the entire research community, thereby reducing the burden on individual sponsors.
Program Activities (Recommendations)
The structure of the DDT programs serves as a series of recommendations for tool developers:
Engage Early and Collaboratively: The programs are designed to provide a framework for early and ongoing scientific collaboration with the FDA to facilitate the development of new tools.
Follow a Staged Process: Developers are guided through a multi-stage process, typically involving a Letter of Intent, a Qualification Plan, and a Full Qualification Package, to systematically build the evidence needed for qualification.
Seek Public Qualification: The ultimate recommendation is to achieve public qualification for a DDT, which makes the tool available for broad use and integrates it into the regulatory review process, expediting future drug development.
Regulatory Considerations
The DDT Qualification Programs are a formal regulatory framework established under the 21st Century Cures Act. A “qualified” DDT has a specific regulatory status; it can be relied upon to have a specific interpretation and application in drug development and regulatory review for its stated Context of Use (COU). This qualification is publicly available and allows the tool to be included in Investigational New Drug (IND), New Drug Application (NDA), or Biologics License Application (BLA) submissions without the FDA needing to reconsider its suitability. This creates a more efficient and predictable regulatory compliance pathway for sponsors who use the qualified tool.
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.
Drug Development Tools (DDTs) are methods, materials, or measures that have the potential to facilitate drug development. Examples of DDTs may include, but are not limited to: a biomarker used for clinical trial enrichment, a clinical outcome assessment (COA) used to evaluate clinical benefit, and an animal model.
Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review.
Once qualified, DDTs will be publicly available to be used in any drug development program for the qualified context of use. Additionally, the qualified DDT generally can be included in IND, NDA, or BLA submissions without needing FDA to reconsider and reconfirm its suitability.
– Drug Development Tool (DDT) Qualification Programs, FDA, 2025
Biomarker qualification
Biomarker Qualification Program
The traditional process of evaluating biomarkers within the context of a single drug development program is inefficient and creates uncertainty for sponsors. This case-by-case approach leads to redundant efforts, slows down the development of novel therapies, and hinders the broad adoption of promising scientific tools. There is a clear need for a centralized, collaborative pathway to formally validate biomarkers, which can de-risk drug development, encourage innovation, and make the process more predictable and cost-effective for all stakeholders.
Recommendations
Drug developers, academic researchers, and other stakeholders should proactively engage with the FDA through the formal Biomarker Qualification Program to validate biomarkers for specific contexts of use. It is recommended to form public-private partnerships and other collaborations to pool resources and data, which strengthens the evidence package for a biomarker’s utility. Developers should use the qualification process to establish a biomarker’s value early, making it a publicly available and reliable tool that can accelerate the development of multiple drug products.
Regulatory Considerations
The Biomarker Qualification Program provides a distinct regulatory pathway for establishing a biomarker’s validity for a specific Context of Use (COU), separate from an individual Investigational New Drug (IND) or New Drug Application (NDA). The process involves a three-stage submission and review cycle: the Letter of Intent, the Qualification Plan, and the Full Qualification Package. Once qualified, a biomarker is publicly listed and can be incorporated into multiple drug development programs without the need for sponsors to re-submit and re-justify the validation data for that specific COU, streamlining subsequent regulatory reviews.
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 mission of the CDER Biomarker Qualification Program (BQP) is to work with external stakeholders to develop biomarkers as drug development tools. Qualified biomarkers have the potential to advance public health by encouraging efficiencies and innovation in drug development.
– Biomarker Qualification Program, FDA, 2025
COA qualification
Clinical Outcome Assessment (COA) Qualification Program
Evaluating patient outcomes on a case-by-case basis within individual drug programs is an inefficient use of resources and creates regulatory unpredictability. This approach frequently leads to redundant efforts to validate the same assessment tools across different development programs. The lack of a standardized, transparent process for accepting Clinical Outcome Assessments (COAs) hinders the development and use of novel, patient-centric endpoints, ultimately slowing the delivery of therapies that address outcomes that matter most to patients.
Recommendations
Developers of COAs, including patient groups, academic researchers, and pharmaceutical sponsors, are encouraged to collaborate with the FDA through the qualification program. This engagement should occur early to ensure that the measures are developed with sufficient rigor to meet regulatory standards. Stakeholders should leverage the program to validate a wide range of COAs, particularly Patient-Reported Outcomes (PROs), making them publicly available to advance patient-focused drug development across the entire industry and reduce redundant validation work.
Regulatory Considerations
The COA Qualification Program offers a formal regulatory pathway for the FDA to review and accept a COA for a specific Context of Use (COU). This qualification is separate from the review of an individual drug application, making the validated tool accessible for any sponsor to use in their clinical trials without re-adjudicating the COA’s fitness for that purpose. Qualification requires a comprehensive submission demonstrating the measure is well-defined and reliable, ensuring that it appropriately captures the patient’s experience or functional status.
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.
COA qualification is a regulatory conclusion that the COA is a well-defined and reliable assessment of a specified concept of interest for use in adequate and well-controlled (A&WC) studies in a specified context of use. COA qualification represents a conclusion that within the stated context of use, results of assessment can be relied upon to measure a specific concept and have a specific interpretation and application in drug development and regulatory decision-making.
– Clinical Outcome Assessment (COA) Qualification Program, FDA, 2025
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.
Developers of DHTs may choose to pursue qualification of DHTs as a DDT or an MDDT for a specific context of use. A qualified DHT may be relied upon in clinical investigations to support submissions for drugs or biological products (if qualified as a DDT) or devices (if qualified as an MDDT) where the context of use is the same (e.g., measurement of a specific clinical event or characteristic in a specific disease population).
– Section III (Regulatory Considerations and Engagement with the Agency), p. 7, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
Developers of DHTs may choose to submit qualification proposals to the appropriate CDER/CBER DDT Qualification Programs (e.g., the COA Program or Biomarker Qualification Program) and/or CDRH’s MDDT Qualification Program. These are voluntary qualification programs that are independent of an individual marketing submission… Sponsors and other stakeholders also may consider submitting DHT-related proposals to the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program.
– Section III (Regulatory Considerations and Engagement with the Agency), p. 7, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
EMA qualification
Questions and answers: Qualification of digital technology-based methodologies to support approval of medicinal products
The EMA emphasizes early engagement to align on regulatory pathways and qualification processes for DHTs.
Context of Use (CoU) is critical in assessing digital technologies, requiring clear justification for their application in clinical trials.
The selection of digital endpoints must demonstrate clinical relevance, reliability, and sensitivity to change.
Validation of digital biomarkers must include data supporting their relationship to clinical outcomes of interest.
Changes to technology during development require a risk-based management approach to maintain the validity of data.
Recommendations
Begin early consultations with the EMA to determine the most suitable regulatory pathways and to define the Context of Use.
Ensure that qualification submissions provide robust evidence on clinical validity, reliability, and sensitivity to change.
Develop best practice guides for the implementation of digital technologies in clinical trials, including training for users and compliance monitoring.
Use an iterative approach for technology qualification, allowing adjustments based on emerging data and findings.
Provide clear risk management strategies for handling technology updates and assessing their impact on data integrity.
Regulatory Considerations
Adhere to applicable regulations, including the Medical Devices Regulation (MDR) and ISO standards, for technologies used in medicinal product development.
Implement data protection measures compliant with EU regulations, ensuring the integrity and security of sensitive health data.
Submit validation documentation demonstrating compliance with Good Clinical Practice (GCP) and Computer System Validation (CSV) standards.
Incorporate statistical planning aligned with ICH guidelines, including pre-planned analyses for endpoints supported by digital technologies.
Engage with multidisciplinary teams and potentially parallel processes with other regulatory agencies (e.g., FDA, PMDA) for a comprehensive qualification 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.
(EMA) The principal focus of the document is to support Qualification of methodologies based on digital technologies in the context of medicinal product development. It may also be of assistance to applicants in the preparation for other types of EMA procedures and interactions, such as Innovation Task Force (ITF) meetings, scientific advice briefing books drafting, and preparation of Marketing Authorisation Applications (MAAs).
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Qualification Opinion for Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy studies
SV95C provides a reliable and sensitive measure of maximal ambulation, addressing limitations of traditional assessments like the 6MWT.
Real-world data collection via wearable devices enhances accuracy and reflects true ambulatory capabilities.
Longitudinal studies confirmed SV95C’s ability to detect disease progression and response to corticosteroid treatments.
Correlations with existing clinical outcome assessments (6MWT, NSAA, and 4SC) validate SV95C’s construct validity.
Patients and caregivers support the use of wearable devices in clinical trials, emphasizing reduced burden and improved trial attractiveness.
Recommendations
Use SV95C as a primary endpoint in DMD clinical trials to monitor maximal stride velocity in real-world conditions.
Incorporate SV95C alongside traditional endpoints to ensure comprehensive assessment of therapeutic efficacy.
Establish training protocols for patients and caregivers to optimize compliance with device usage.
Expand normative data for SV95C in younger and more diverse patient populations.
Conduct further research on meaningful change thresholds (MCTs) to refine clinical relevance.
Regulatory Considerations
Ensure SV95C is included as a primary endpoint with supporting secondary endpoints (e.g., muscle strength assessments) for consistency.
Validate wearable devices used for SV95C measurement to meet regulatory standards for accuracy and reliability.
Address variability and standardize protocols for data collection to ensure regulatory compliance.
Collect additional longitudinal data to strengthen the predictive value of SV95C for regulatory submissions.
Incorporate privacy and data security measures to comply with data protection regulations, including anonymization and encryption.
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 European Medicines Agency (EMA) in 2023 qualified a stride velocity 95th centile measure (from a wearable sensor) as an acceptable primary endpoint in Duchenne muscular dystrophy trials. This document explains that decision.
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Once you’ve read the guidances, explore these best practices from the field:
Industry spotlight
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