CENTER FOR DRUG EVALUATION AND RESEARCH

INNOVATION PREDICTABILITY ACCESS

March 2023

Framework for the Use of Digital 

Health Technologies in Drug and 

Biological Product Development 
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 1

Table of Contents

Introduction ............................................................................ 2

Definitions ............................................................................................... 3

Scope ....................................................................................................... 3

Background ............................................................................. 5

Regulatory Background .............................................................................5

Current Landscape of DHTs .......................................................................6

Addressing Challenges Related to the Use of DHTs in Regulatory 

Decision-Making for Drugs....................................................... 8

Internal Programs.....................................................................................8

1. DHT Steering Committee.....................................................................8

2. Technical Expertise and Training ........................................................9

a. Verification and Validation ...........................................................9

b. Use of a Participant’s Own DHT or General-Purpose 

 Computing Platform .................................................................. 10

c. Upgrades and Updates of DHTs in Drug Development ................... 10

d. Artificial Intelligence and Machine Learning................................ 10

e. Technical Consultation of Experts and Staff Training .................... 11

3. Consistency of Evaluations Across Review Divisions............................. 11

4. Statistical Considerations in the Analysis of DHT-Derived Data ............ 11

5. IT Capabilities................................................................................... 11

External Programs ...................................................................................12

1. FDA Meetings With Sponsors..............................................................12

2. Drug Development Tool Qualification Program ....................................12

3. Guidance ..........................................................................................13

4. Public Meetings ............................................................................... 14

5. Demonstration Projects .....................................................................15

6. External Organizations ..................................................................... 16

Conclusion.............................................................................. 17
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 2

Introduction

The Prescription Drug User Fee Act VII (PDUFA VII) commitment letter represents 

the product of discussions between the Food and Drug Administration (FDA), 

regulated industry, and public stakeholders, as mandated by Congress.1

 The 

performance and procedural goals and other commitments specified in the PDUFA 

VII commitment letter apply to aspects of the human drug2

 review program that 

are important for facilitating timely access to safe, effective, and innovative new 

medicines for patients. The commitment letter includes goals relating to the use 

of digital health technologies (DHTs) to support drug development and review.3

Among other activities relating to the use of DHTs, under section IV.C.1 of the commitment letter, FDA has established a Framework for the Use of DHTs in Drug and 

Biological Product Development to guide the use of DHT-derived data in regulatory 

decision-making for drugs (hereinafter “Framework”).

This document outlines the Framework that FDA will use to implement a multifaceted 

DHT program for drugs. The DHT program will include workshops and demonstration projects; engagement with stakeholders; establishment of internal processes to 

support the evaluation of DHTs for use in drug development; promotion of shared 

learning and consistency regarding DHT-based policy, procedure, and analytic tool 

development; and publication of guidance documents. This document is not a guidance document and does not propose or establish policies.

1 PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 through 2027, 

available at https://www.fda.gov/media/151712/download.

2 For the purposes of the Framework, the terms drug or drugs include human drugs and biological 

products unless otherwise noted.

3 See section IV.C of the PDUFA VII commitment letter, “Enhancing Use of Digital Health 

Technologies to Support Drug Development and Review.”
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 3

Definitions

For the purposes of the Framework, DHTs are systems that use computing platforms, 

connectivity, software, and/or sensors for health care and related uses. They include 

technologies intended for use as a medical product, in a medical product, or as an 

adjunct to other medical products (devices, drugs, and biologics). DHTs may also be 

used to develop or study medical products. There is a large spectrum of DHTs available for potential use to support drug development and review, some of which meet the 

definition of a device under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 

others that do not.4

 DHTs may take the form of hardware and/or software. DHTs often 

consist of sensor hardware that allows for continuous or intermittent recording of physiological and/or behavioral data (e.g., blood pressure, physical activity, glucose levels). 

DHTs can also be software applications that are run on general-purpose computing 

platforms (e.g., mobile phone, tablet, or smart watch). These DHTs may be used to 

administer electronic clinical outcome assessments, including electronic patientreported outcome and electronic performance outcome instruments. Some DHTs 

consist of hardware and software (e.g., a continuous glucose monitoring device that 

includes a sensor and a mobile application), both of which are necessary to achieve 

the DHT’s intended function or functions.

Scope

The Framework includes the following activities outlined in the PDUFA VII 

commitment letter: 

• Establishing a steering committee, including members from the Center for Drug 

Evaluation and Research (CDER), the Center for Biologics Evaluation and 

Research (CBER), the Oncology Center of Excellence (OCE), the Office of the 

Commissioner, and the Center for Devices and Radiological Health (CDRH) and 

its Digital Health Center of Excellence (DHCoE),5

 to ensure consistent policy 

across FDA regarding the use of DHT-derived data in regulatory decision-making 

for drugs 

• Convening public meetings or workshops with key stakeholders, including 

patients, biopharmaceutical companies, DHT companies, and academia, 

to gather input into issues related to the use of DHTs in regulatory 

decision-making 

• Identifying demonstration projects to inform methodologies for efficient DHT

evaluation 

4 See section 201(h) of the FD&C Act for the definition of a device. How to determine whether a DHT 

proposed for use meets the definition of a device under the FD&C Act is outside the scope of this 

Framework. For further information about FDA digital health regulatory policies, see

https://www.fda.gov/medical-devices/digital-health-center-excellence/ask-question-about-digitalhealth-regulatory-policies.

5 For further information about the CDRH DHCoE and available resources, see 

https://www.fda.gov/medical-devices/digital-health-center-excellence.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 4

• Publishing guidance documents for drugs on the use of DHTs in traditional 

and decentralized clinical trials (DCTs) and in other areas as identified through 

stakeholder engagement 

• Publishing guidance on regulatory considerations for prescription drug use-related software that includes information about software that is disseminated by 

a drug applicant for use with a prescription drug or biologic product that may 

be described in labeling, including prescribing information

• Enhancing consistency across centers with regards to the development, use, 

and review of DHTs and associated endpoints through building technical expertise and review capacity, providing staff training in evaluation of DHTs, and 

developing statistical methodology regarding DHT-derived clinical endpoints

• Enhancing IT capabilities to support the review of DHT-generated data
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 5

Background

Regulatory Background

In December 2021, FDA published the draft guidance for industry, investigators, 

and other stakeholders Digital Health Technologies for Remote Data Acquisition 

in Clinical Investigations.

6

 This guidance outlines recommendations intended to 

facilitate the use of DHTs in clinical investigations, as appropriate, for the evaluation of medical products. These recommendations address selection of suitable 

DHTs, verification and validation of DHTs, and use of DHTs to collect data for trial 

endpoints. The guidance also addresses some of the risks associated with the use 

of DHTs in clinical investigations and their management. As noted, this is a draft 

guidance. When final, draft guidances will represent FDA’s current thinking on their 

respective topics.

Many of the DHTs that can be used as tools to support drug development were 

originally developed and used as medical devices or general wellness products, 

and FDA (more specifically, CDRH and its DHCoE) has provided guidance on a 

number of topics relating to such products. This includes guidances that address 

mobile medical applications,7

 general wellness,8 third-party off-the-shelf software 

used in medical devices,9

 clinical evaluation of software as a medical device,10

6 Digital Health Technologies for Remote Data Acquisition in Clinical Investigations | FDA

7 Policy for Device Software Functions and Mobile Medical Applications | FDA

8 General Wellness: Policy for Low Risk Devices | FDA

9 Off-The-Shelf Software Use in Medical Devices | FDA

10 Software as a Medical Device (SAMD): Clinical Evaluation | FDA
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 6

information used to review medical device software,11 considerations for changes 

to medical device software,12 device interoperability for information sharing across 

systems,13 multiple function device products,14 and cybersecurity considerations for 

medical devices.15

Building on its longstanding commitment to advancing innovative approaches to 

DHTs, FDA issued a discussion paper in 201916 and an Action Plan17 in 2021 focused 

on artificial intelligence (AI)-enabled medical devices to provide a holistic approach 

to the subset of DHTs that are enabled by machine learning. FDA has also published 

guidance to support patient-focused drug development,18 which may include the 

use of DHTs. In addition, FDA has hosted numerous workshops19 and patient 

engagement advisory committee20 meetings on DHT-related topics and has engaged 

in stakeholder outreach activities through participation in public-private partnerships 

(e.g., the Medical Device Innovation Consortium),21 as well as collaborative communities22 with a DHT focus.

Current Landscape of DHTs

DHTs include technologies such as wearable, implantable, ingestible, and environmental sensors and software applications on mobile phones, among others. Advances 

in sensor technology, general-purpose computing platforms, and methods for data 

capture, transmission, and storage have revolutionized the ability to remotely obtain 

and analyze clinically relevant information from individuals. DHTs used for remote data 

acquisition are playing a growing role in health care and offer important opportunities in 

clinical research. DHTs can support traditional site-based clinical trials and enable the 

conduct of DCTs, which are clinical investigations where some or all trial-related activities occur at locations other than traditional clinical trial sites. DHT software can also be 

disseminated for use with a prescription drug. 

11 Content of Premarket Submissions for Device Software Functions | FDA

12 Deciding When to Submit a 510(k) for a Software Change to an Existing Device | FDA

13 Design Considerations and Pre-market Submission Recommendations for Interoperable Medical 

Devices | FDA

14 Multiple Function Device Products: Policy and Considerations | FDA

15 Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket 

Submissions | FDA

16 Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-

Based Software as a Medical Device (SaMD) - Discussion Paper and Request for Feedback | FDA

17 Artificial Intelligence and Machine Learning (AI/ML) Software as a Medical Device Action Plan | FDA

18 Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical 

Outcome Assessments | FDA 

19 For example, Public Workshop - Evolving Role of Artificial Intelligence in Radiological Imaging, 

Virtual Public Workshop - Transparency of Artificial Intelligence/Machine Learning-enabled Medical 

Devices, and Virtual Public Meeting - Patient-Generated Health Data Throughout the Total Product 

Life Cycle of Medical Devices

20 CDRH Patient Engagement Advisory Committee | FDA

21 https://mdic.org

22 Collaborative Communities: Addressing Health Care Challenges Together

Using the power 

of modern 

communication 

technology, 

miniaturization 

of electronic 

sensors, and 

mobile computing 

platforms, digital 

health technologies 

offer extraordinary 

opportunities to 

gather clinical 

data directly from 

patients.

Leonard Sacks, M.D., 

Associate Director for 

Clinical Methodology, 

OMP/CDER/FDA
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 7

Compared to scheduled trial visits, which require a participant to travel to a site, the 

use of DHTs to remotely collect data from trial participants may allow for more frequent or even continuous data collection, with reduced burden on trial participants. 

The technology exists to allow data derived from DHTs to be transmitted directly to 

investigators, sponsors, and/or other authorized parties, with the capability to maintain blinding or masking when appropriate. By reducing the burden on trial participants, DHTs may increase trial recruitment rates, help retain participation over 

longer periods of time, and increase participant diversity. Remote data collection 

may also prove useful in situations where face-to-face care or interaction is limited 

or unavailable (e.g., during a pandemic).

DHTs may also provide opportunities to collect data directly from trial participants 

who are performing daily activities (e.g., ambulation, sleep, everyday tasks) wherever the participants may be (e.g., home, school, work, outdoors). Moreover, 

DHTs may facilitate the collection of information from participants who are unable 

to report their experiences (e.g., infants, cognitively impaired individuals). These 

features may provide a broader picture of how participants feel or function in their 

daily lives by providing ways of measuring clinical characteristics or clinical events 

(e.g., hypertensive events, tremors, or acute hypoglycemia) that would otherwise 

be unavailable or impractical without the use of DHTs. 

However, to use any measurement of clinical characteristics or clinical events as 

endpoints in clinical investigations intended to support drug development, approaches are needed to determine the clinical meaning and significance of these 

measurements to patients, caregivers, and healthcare providers. In addition, while 

remote data acquisition may increase opportunities for individuals to participate 

in clinical investigations remotely, it may raise issues including data privacy and 

confidentiality concerns. 
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 8

Addressing Challenges Related to the Use 

of DHTs in Regulatory Decision-Making 

for Drugs

The successful utilization of DHTs to support drug development and review will 

depend on FDA and other stakeholders addressing the challenges discussed 

throughout the Framework. This Framework includes programs to support DHT-related activities within FDA (internal programs) and programs to engage industry 

and other stakeholders (external programs) in the development and use of DHTs.

Internal Programs

FDA has established the DHT Steering Committee which will utilize this Framework 

to develop internal programs to build review capacity and expertise and will help 

ensure consistent review policies regarding the use of DHTs for drug development. 

1. DHT Steering Committee 

 The DHT Steering Committee will oversee the implementation of the PDUFA 

VII commitments related to evaluating DHT-based measurements in human 

drug development to support new drug applications, biologics license applications, supplements to those applications, and drug safety monitoring by 

helping to ensure that DHT-based data are fit for the intended purpose. The 

DHT Steering Committee has overseen the design of the Framework and 

will serve as the guiding body on activities and policy development related 

to DHTs. The DHT Steering Committee will also serve as a forum for shared 
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 9

communication about DHT use in drug development as well as provide recommendations to promote consistency across centers regarding DHT-based 

policies, procedures, and analytic tools development.

 The DHT Steering Committee consists of senior staff from CDER, CBER, 

and CDRH, including the DHCoE, as well as OCE and the Office of Clinical 

Policy and Programs. The DHT Steering Committee will do the following:

• Make recommendations and support implementation of PDUFA VII 

commitments regarding DHTs (e.g., public meetings, guidance 

documents, demonstration projects, technology needs, training)

• Gather information about the present state of DHTs, including specific 

challenges in their use

• Make policy recommendations impacting the use and evaluation of 

DHT-based measurements in human drug development

• Oversee activities to assist organizational units with consistent approaches 

to the review of drug submissions that contain DHT-derived data

• Oversee and coordinate DHT-related drug development working groups 

and teams across CDER and CBER, as appropriate

• Engage with external stakeholders on DHT-related issues in human 

drug development

More information about the DHT Steering Committee and its work will be 

published on the FDA website.

2. Technical Expertise and Training 

 The Agency will build on its technical expertise and develop training within the human drugs and biological products programs to enhance internal 

knowledge regarding the use of DHTs in drug development. Areas of focus 

will include the following: 

a. Verification and Validation 

Verification and validation are processes to ensure DHTs are accurate and 

reliable and meet intended users’ needs. For the purposes of this Framework, verification is confirmation by examination and provision of objective 

evidence that the physical parameter that the DHT measures (e.g., acceleration, temperature, pressure) is measured accurately and precisely. Validation 

is confirmation by examination and provision of objective evidence that the 

selected DHT appropriately assesses the clinical event or characteristic in 

the proposed participant population. Verification is often viewed as part of 

the validation process. Usability and interoperability studies may be included 

as part of validation. Assessment of DHT verification and validation requires 

domain-specific expertise, including in statistics, mathematics, and generalpurpose computing platforms.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 10

b. Use of a Participant’s Own DHT or General-Purpose Computing Platform 

 FDA will build on its expertise in general-purpose computing platforms (e.g., 

mobile phones or smartwatches) to address participants’ use of their own 

DHTs in a clinical investigation. Challenges in the evaluation of personal 

DHTs or general-purpose computing platforms may relate to consistency, 

accuracy, and/or precision. Minimum technical specifications (e.g., for operating systems, storage capacity, and sensor performance) and performance 

specifications (e.g., accuracy and precision for measuring specified clinical 

events or characteristics) will be important to ensure the measurements are 

consistent across different protocol-specified DHTs.

c. Upgrades and Updates of DHTs in Drug Development

 During clinical investigations, new models of DHTs may become available, 

and existing DHTs may require software updates. FDA will build its expertise in understanding the impact of updates or changes to DHTs. Technical 

experts and statisticians across centers will collaborate and assess whether 

there is a meaningful difference in results observed before and after the 

updates to a DHT and how the differences impact interpretability of those 

results in their context of use.

d. Artificial Intelligence and Machine Learning 

 AI is a branch of computer science, statistics, and engineering that uses algorithms or models to perform tasks and exhibit behaviors such as learning, 

making decisions, and making predictions. The subset of AI known as machine learning (ML) allows models to be developed by training algorithms 

through analysis of data, without models being explicitly programmed.23 AI 

can use different techniques, including models based on statistical analysis of data and knowledge-based systems that primarily rely on rules (e.g., 

if-then statements and ML). DHTs may incorporate the use of AI algorithms 

that have the potential to transform health care by deriving new and important insights from the vast amount of data generated by DHTs. There are 

numerous possibilities to incorporate DHTs using AI algorithms into drug 

development, including participant recruitment, site selection, clinical trials 

data collection and analysis, and safety monitoring. FDA intends to build 

on its domain-specific expertise in data science, informatics, statistics, and 

mathematics to help ensure the appropriate application of AI technology in 

the context of DHTs used for drug development.

23 See International Medical Device Regulators Forum, Machine Learning-enabled Medical Devices: 

Key Terms and Definitions, available at https://www.imdrf.org/sites/default/files/2022-05/IMDRF%20

AIMD%20WG%20Final%20Document%20N67.pdf.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 11

e. Technical Consultation of Experts and Staff Training 

 To facilitate our work in the areas described above, FDA intends to enhance 

our relevant expertise through hiring new staff, training existing staff, and 

consulting with internal and external experts, as appropriate. The DHT 

Steering Committee will support development of a training program for 

drug reviewers to enhance their expertise in the review of submissions that 

include information relating to the use of DHTs.

3. Consistency of Evaluations Across Review Divisions

 A single DHT measurement may be used for studies of different diseases 

and different drugs. For example, actigraphy is widely used to evaluate 

functionality and may be used in a broad range of conditions, including cardiorespiratory diseases, neuromuscular diseases, and psychiatric diseases. 

Review divisions and centers should have consistent approaches to the 

review and evaluation of submissions that contain DHT-related data. The 

DHT Steering Committee will help facilitate consistent approaches to the 

review and evaluation of such submissions. 

4. Statistical Considerations in the Analysis of DHT-Derived Data

 Although use of DHTs in clinical investigations has increased, few clinical 

investigations have used sensor-based DHTs to support primary or secondary endpoints. The use of DHT-derived endpoints presents unique statistical considerations for FDA during their review. These considerations are 

related to data quality; technical data specifications; provenance (i.e., understanding the lineage of the data); definitions used (e.g., activity counts, 

steps, calories); techniques and algorithms used for processing, summarizing, and analyzing DHT data; and treatment of missing data. Existing and 

novel statistical methods for validating DHT-derived data need to be assessed. FDA will leverage its statistical expertise to address novel analytical 

considerations for endpoints derived from DHT data. In addition, FDA will 

consider developing technical data specifications to facilitate submission of 

readily analyzable DHT-derived data supporting drug development.

5. IT Capabilities 

 Large DHT-generated datasets introduce new challenges regarding the 

ability to receive and analyze data to support a regulatory decision. Through 

PDUFA VII, FDA will enhance its IT capabilities to support the review of 

DHT-generated data. This work will be coordinated with other IT capability 

development activities across the Agency.

• FDA will enhance its internal systems to support review of DHT-related 

submissions, including capturing key information about clinical trials 

utilizing DHTs to support tracking the number and rate of change of 

DHT-related submissions. To facilitate tracking, CDER and CBER plan to 

request that sponsors and applicants identify when submissions contain 
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 12

information related to the use of DHTs. FDA will develop internal systems 

to monitor trends in submissions containing DHT-related data.

• FDA will establish a secure cloud technology to enhance its infrastructure and analytics environment that will enable FDA to effectively 

receive, aggregate, store, and process large volumes of data from drug 

trials conducted using DHTs. FDA will utilize the cloud environment to 

meet review needs across CDER and CBER.

 • After establishing the cloud environment, FDA will pilot a 

secure, cloud-based mechanism to support submission and 

review of DHT-generated datasets. 

• FDA will work to enhance, recommend, and implement standards that 

reduce the handling necessary to make DHT data analyzable. CDER 

and CBER intend to collaborate with the DHCoE to promote the development and adoption of data standards for DHT-generated datasets.

External Programs

The Framework describes a range of activities for FDA to engage with external stakeholders, such as sponsors, patient advocacy groups, DHT companies, clinical investigators, international regulatory bodies, and professional societies. Such activities can 

help FDA better understand the challenges and opportunities associated with DHTs 

and will include holding public meetings, running demonstration projects, and publishing guidance on the use of DHTs to support drug development and review. 

1. FDA Meetings With Sponsors

 Engagements between sponsors and FDA regarding the use of DHTs may 

occur at different stages of drug development and may include meetings with 

the DHT Steering Committee, Critical Path Innovation Meetings, pre-IND 

meetings, pre-submissions meetings, IND and NDA review meetings, and 

related meetings and communications.24 Topics for discussion may include 

the regulatory status of DHTs, development of trial endpoints, selection of 

DHTs for clinical investigations, and verification and validation of DHTs. 

2. Drug Development Tool Qualification Program

FDA has qualification programs that are intended to support the development 

of tools for use in assessing medical products and that provide another avenue 

for sponsors and other stakeholders to engage with the Agency. Developers of 

DHTs may choose to pursue qualification of DHTs as drug development tools 

24 Sponsors should follow each FDA center’s procedures for engaging with the Agency in the context 

of a development program. For drugs and biological products, see the web page for Critical Path 

Innovation Meetings, available at https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecularentities-and-new-therapeutic-biological-products/critical-path-innovation-meetings-cpim; the draft 

guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA 

Products (December 2017); and the draft guidance for industry Formal Meetings Between the FDA and 

Sponsors or Applicants of BsUFA Products (June 2018). For further information about FDA digital health 

regulatory policies, see https://www.fda.gov/medical-devices/digital-health/ask-question-about-digitalhealth-regulatory-policies.

1.

2.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 13

(DDTs)25 for a specific context of use. A qualified DHT may be relied upon in 

multiple clinical investigations to support premarket submissions for drugs (if 

qualified as a DDT) where the context of use is the same (e.g., measurement 

of a specific outcome in a specific disease population), without having to repeat 

studies that supported the qualification, provided that the qualification has not 

been rescinded or modified. FDA’s DDT Committee reviews requests for DHTs 

seeking qualification as a DDT. The DDT Committee and the DHT Steering 

Committee will work together to help ensure alignment and avoid overlap of 

responsibilities. 

3. Guidance

 To facilitate the appropriate use of DHTs in drug development, FDA has 

published draft guidances that, when finalized, will reflect FDA’s current 

thinking on a number of DHT topics, and the Agency plans to develop 

additional guidance documents. 

 Draft guidance for industry, investigators, and other stakeholders

Digital Health Technologies for Remote Data Acquisition in Clinical 

Investigations (December 2021)

25 See CDER’s web page for Drug Development Tool (DDT) Qualification Programs, available 

at https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddtqualification-programs.

New capabilities for 

measuring function 

and symptoms 

continuously and 

in routine life 

settings could 

enable significant 

improvements in 

the degree to which 

data reflect the 

actual status of the 

research participant.

Robert M. Califf, M.D., 

Commissioner U.S. Food 

and Drug Administration

3.

• Selection of DHTs that are suitable for use in clinical investigations

• Verification and validation of DHTs for use in clinical investigations

• Use of DHTs to collect data for trial endpoints 

• Identification of risks associated with the use of DHTs during clinical 

investigations

• Management of risks related to the use of DHTs in clinical investigations

Draft guidance for industry Electronic Systems, Electronic Records, 

and Electronic Signatures in Clinical Investigations: Questions and 

Answers (March 2023) 

Part 11 is intended to ensure the authenticity, integrity, and confidentiality of 

electronic records from their point of creation to their modification, maintenance, archiving, retrieval, or transmission. The draft guidance addresses commonly asked questions about the applicability of part 11 to electronic records, 

electronic signatures, and electronic systems used in clinical investigations, 

including use of DHT-derived data. The draft guidance proposes recommendations related to access controls, data provenance and traceability, secure data 

transfers, and archiving of derived data related to DHT use in clinical trials. 

This draft guidance outlines proposed recommendations intended to facilitate 

the use of DHTs in clinical investigations, as appropriate, for the evaluation of 

medical products. These recommendations address the following topics:
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 14

Draft guidance for industry, investigators, and other stakeholders

Decentralized Clinical Trials for Drugs, Biological Products, and Devices

FDA plans to publish this draft guidance in 2023. This guidance will include 

recommendations to clarify and advance the use of decentralized clinical 

trials to support the development of drugs and devices.

Draft guidance for industry Regulatory Considerations for Prescription Drug Use-Related Software (targeted for publication by end of 

fiscal year 2023 per commitment letter)

As stated in the PDUFA VII commitment letter, prescription drug use-related 

software is software that is disseminated by a drug applicant for use with a 

prescription drug or biologic product or with a drug- or biologic-led combination 

product. This draft guidance will cover how such software may be described in 

labeling, including in the Prescribing Information, when the software is distributed with a drug or integrated as part of a drug- or biologic-led combination product, as well as when the software is distributed by an applicant independent of 

an approved product.

Additional DHT-related guidances

The DHT Steering Committee will address areas where additional guidance 

may be beneficial. Consistent with good guidance practices, guidance topics will be informed by stakeholder engagement, including interactions with 

sponsors, DHT companies, and patient advocacy groups. Public meetings 

and demonstration projects will also serve to identify topic areas of public 

health importance. As stated in the PDUFA VII commitment letter, beginning 

in fiscal year 2024, FDA will publish additional draft guidances in identified 

areas of need informed by stakeholder engagement. 

4. Public Meetings 

By the end of the second quarter of fiscal year 2023, FDA will convene the 

first of a series of five public meetings or workshops with key stakeholders, 

including patients, biopharmaceutical companies, DHT companies, and 

academia, to gather input on issues related to the use of DHTs in regulatory 

decision-making related to drug and biological product development. The 

meetings and workshops will be designed to address the following topics: 

• Understanding priorities for the development of DHTs to support clinical 

investigations

The public meeting will explore improving patient access, 

increasing diversity, and facilitating engagement through remote 

trial-related measurements. It will also cover patient and industry 

perspectives, opportunities for remote data acquisition (e.g., 

actigraphy) from trial participants, and the use of DHTs to 

measure clinical outcomes. 
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 15

• Identifying approaches to DHT verification and validation

The public meeting will explore approaches to verification and validation 

of various types of technologies for different patient populations and diseases. Such approaches may be helpful to demonstrate that the clinical 

event or characteristic to be assessed (e.g., step count or heart rate) is 

consistently and appropriately measured in the population of interest. 

• Understanding DHT data processing and analysis to inform the need 

for novel analytical techniques

The public meeting will consider statistical challenges and issues related 

to the use and analysis of DHT-derived data. Challenges addressed at 

the meeting could include aggregation, analysis, interpretation, and 

reporting of continuously measured DHT data as well as handling of 

associated missing data. 

• Addressing the regulatory acceptance of safety monitoring tools that 

utilize AI and ML-based algorithms for pharmacovigilance purposes 

(e.g., continuous data streams from DHTs)

The public meeting will cover AI for detecting adverse events (e.g., 

seizures, hypoglycemia) using DHTs and issues related to source data 

and algorithms. 

• Understanding emerging issues

Over the next few years, as new issues emerge and as FDA learns more 

about the challenges related to the use of DHTs in clinical investigations 

and regulatory decision-making, a final public meeting topic will be determined to enhance FDA’s ability to support drug development programs 

that use DHTs. 

5. Demonstration Projects

 FDA will identify at least three issue-focused demonstration projects to 

inform methodologies for efficient DHT evaluation in drug development. 

These projects may involve engagement with researchers from academia, 

the biopharmaceutical industry, patient groups, and other stakeholders. 

They will cover key issues to inform regulatory policy development and 

provide regulatory advice. The focus of these projects may include validation methods for specific technologies, endpoint development, analytic 

approaches to missing data, use of multi-channel inputs to characterize an 

endpoint, evaluation of continuous data versus discrete measurements, use 

and limitations of DHTs in DCTs, and other related issues.

5.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 16

6. External Organizations

 Development of DHTs is a rapidly growing commercial enterprise involving, 

among others, technology companies, manufacturers of medical devices, 

and manufacturers of consumer technologies that measure health and wellness. Many developers have emerged that are focused on advancing the use 

of DHTs in clinical research, including external organizations such as publicprivate partnerships, consortiums, professional organizations, and trade 

groups. FDA will look to continue engagement with such external organizations to facilitate meeting the objectives included in this Framework.

FDA has participated in several forums organized by the National Academies 

of Sciences, Engineering, and Medicine; the Drug Information Association; 

the Heart Failure Collaboratory; and other professional bodies addressing the 

use of DHTs in drug development.

6.
Framework for the Use of Digital Health Technologies in Drug and Biological Product Development 17

Conclusion

DHTs may provide opportunities for more efficient drug development. DHTs and 

DHT-derived data can be important tools in supporting timely access to safe, effective, 

and innovative new medicines for patients. DHTs can be used to increase decentralization of trial-related activities, improve patient access to trials, increase trial diversity, 

and promote retention by facilitating remote trial-related measurements. In addition, 

DHTs can facilitate direct collection of information from participants who are unable to 

report their experiences (e.g., infants, cognitively impaired individuals). Further, they 

may allow for development of novel endpoints, which can provide a broader picture of 

how participants feel or function in their daily lives. Despite the potential advantages of 

DHTs, many challenges arise when incorporating DHTs and DHT-derived data into regulatory decision-making. This Framework outlines a multifaceted approach to collaboratively address these challenges with our stakeholders. Through these joint efforts, we 

intend to advance the development of drugs and promote the public health.

Integrating research 

and clinical care 

with access to 

digital information 

presents enormous 

potential to benefit 

the research 

enterprise and 

health outcomes.

Robert M. Califf, M.D., 

Commissioner U.S. Food 

and Drug Administration
U.S. Food and Drug Administration

www.fda.gov