Notice2025-06967
Exploration of Health Level Seven Fast Healthcare Interoperability Resources for Use in Study Data Created From Real-World Data Sources for Submission to the Food and Drug Administration; Establishment of a Public Docket; Request for Comments
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Published
April 23, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or the Agency) is announcing the establishment of a docket for public comments exploring the Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) for submission of data collected from real-world data (RWD) sources. In alignment with the new Department of Health and Human Services (HHS), Assistant Secretary for Technology Policy/Office of the National Coordinator for Health (ASTP/ONC) policy on health information technology (health IT), the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are exploring approaches to optimize the submission of structured and standardized clinical study data collected from RWD sources. FDA is seeking public comment from interested parties on specific questions. Interested parties may include regulated industry, health IT vendors, academic medical centers, and electronic data capture vendors as well as other interested parties.
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<title>Federal Register, Volume 90 Issue 77 (Wednesday, April 23, 2025)</title>
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[Federal Register Volume 90, Number 77 (Wednesday, April 23, 2025)]
[Notices]
[Pages 17067-17069]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-06967]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-N-0287]
Exploration of Health Level Seven Fast Healthcare
Interoperability Resources for Use in Study Data Created From Real-
World Data Sources for Submission to the Food and Drug Administration;
Establishment of a Public Docket; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; establishment of a public docket; request for comments.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the establishment of a docket for public comments exploring
the Health Level Seven (HL7) Fast Healthcare Interoperability Resources
(FHIR) for submission of data collected from real-world data (RWD)
sources. In alignment with the new Department of Health and Human
Services (HHS), Assistant Secretary for Technology Policy/Office of the
National Coordinator for Health (ASTP/ONC) policy on health information
technology (health IT), the Center for Drug Evaluation and Research
(CDER) and the Center for Biologics Evaluation and Research (CBER) are
exploring approaches to optimize the submission of structured and
standardized clinical study data collected from RWD sources. FDA is
seeking public comment from interested parties on specific questions.
Interested parties may include regulated industry, health IT vendors,
academic medical centers, and electronic data capture vendors as well
as other interested parties.
DATES: Either electronic or written comments on the notice must be
submitted by June 23, 2025.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of June 23, 2025. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2025-N-0287 for ``Exploration of Health Level Seven Fast Healthcare
Interoperability Resources for Use in Study Data Created From Real-
World Data Sources for Submission to the Food and Drug Administration;
Establishment of a Public Docket; Request for Comments.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Ethan Chen, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Silver Spring, MD 20993-0002, 301-796-7626, <a href="/cdn-cgi/l/email-protection#3356475b525d1d505b565d735557521d5b5b401d545c45"><span class="__cf_email__" data-cfemail="0663726e676828656e636846606267286e6e7528616970">[email protected]</span></a>, or
Hussein Ezzeldin, Center for Biologics Evaluation and Research, Food
and Drug Administration, 10903
[[Page 17068]]
New Hampshire Ave., Silver Spring, MD 20993-0002, 240-402-8629,
<a href="/cdn-cgi/l/email-protection#e68e939595838f88c8839c9c838a828f88a6808287c88e8e95c8818990"><span class="__cf_email__" data-cfemail="721a070101171b1c5c170808171e161b1c321416135c1a1a015c151d04">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Sponsors are increasing their use of RWD to support claims of
safety and effectiveness for FDA-regulated medical products. FDA
defines RWD as ``data relating to patient health status and/or the
delivery of health care routinely collected from a variety of sources.
Examples of RWD include data derived from electronic health records,
medical claims data, data from product or disease registries, and data
gathered from other sources (such as digital health technologies) that
can inform on health status'' (Ref. 1).
As stated in FDA's guidance for industry entitled ``Data Standards
for Drug and Biological Product Submissions Containing Real-World
Data'' (Data Standards Guidance) (Ref. 2), the Agency recognizes
challenges involved in standardizing clinical study data collected from
RWD sources for inclusion in applicable submissions. The Agency is
currently considering how data standards specific to data derived from
RWD sources might help accurately and consistently represent data
obtained from RWD sources when submitting study data to the Agency.
FDA will also consider the recently adopted HHS Health IT Alignment
Policy (Ref. 3), which requests that all HHS operating and staff
divisions (including FDA) align on health IT policy that is being
developed and implemented by ASTP/ONC. ASTP/ONC defines health IT as
``hardware, software, integrated technologies or related licenses,
intellectual property, upgrades, or packaged solutions sold as services
that are designed for or support the use by health care entities or
patients for the electronic creation, maintenance, access, or exchange
of health information'' (Ref. 3). The policy asks for ``greater
alignment of health IT-related activities in support of [HHS'] health
IT and interoperability goals'' (Ref. 3) and, as such, creates an
opportunity for FDA to explore such alignment with respect to clinical
study data collected from RWD sources.
In 2020, the final rule entitled ``21st Century Cures Act:
Interoperability, Information Blocking, and the ONC Health IT
Certification Program'' (85 FR 25642; May 1, 2020) was published by
ASTP/ONC, establishing the HL7 FHIR standard as a nationwide standard
for access, exchange, and use of data for healthcare delivery
organizations. The capabilities that the final rule requires from ONC-
certified health IT will enable patients, clinicians, researchers, and
other appropriate parties to access data from certified electronic
health records (EHRs) and other certified health IT in a
Representational State Transfer manner, utilizing application
programming interface (API) technology. Beginning in 2022, more than 50
data elements in the United States Core Data for Interoperability
(USCDI) are consistently and routinely available through certified
health IT using FHIR (see <a href="https://www.healthit.gov/isp/united-states-core-data-interoperability-uscdi#uscdi-v1">https://www.healthit.gov/isp/united-states-core-data-interoperability-uscdi#uscdi-v1</a>). The data elements contain a
wide array of clinical concepts, including patient demographics, vital
signs, laboratory tests, and unique identifiers for patient implantable
devices.\1\
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\1\ An example of adoption of FHIR is the ``Centers for Medicare
& Medicaid Services (CMS) Interoperability and Prior Authorization''
final rule published February 8, 2024 (89 FR 8758), furthering the
implementation of FHIR across the Federal government for multiple
use cases. See <a href="https://www.cms.gov/newsroom/fact-sheets/cms-interoperability-and-prior-authorization-final-rule-cms-0057-f">https://www.cms.gov/newsroom/fact-sheets/cms-interoperability-and-prior-authorization-final-rule-cms-0057-f</a>.
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ASTP/ONC expanded the number of data elements available through the
FHIR standard in the final rule entitled ``Health Data, Technology, and
Interoperability: Certification Program Updates, Algorithm
Transparency, and Information Sharing'' (HTI-1 final rule) published
January 9, 2024 (89 FR 1192). The HTI-1 final rule establishes USCDI
version 3, a data set of more than 80 data elements, as the new
standard set of data classes and constituent data elements for
nationwide, interoperable health information exchange. Additionally,
ASTP/ONC has also created the Trusted Exchange Framework and Common
Agreement (TEFCA), which operates in the United States as a nationwide
framework for health information sharing.\2\
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\2\ See <a href="https://www.healthit.gov/topic/interoperability/policy/trusted-exchange-framework-and-common-agreement-tefca">https://www.healthit.gov/topic/interoperability/policy/trusted-exchange-framework-and-common-agreement-tefca</a>.
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Although clinical study data submitted to FDA are not explicitly
required to be collected or submitted using ONC-certified health IT,
given the fact that some RWD sources (such as EHRs) are already
adopting FHIR and support the USCDI standardized data elements, FDA
will explore the possibility of receiving clinical study data that
includes data collected from EHRs using HL7 FHIR (along with other data
standards currently used in clinical research). The Agency has actively
explored many exchange formats and data standards and terminologies
that have gained maturity in the past decade for potential adoption.
Current initiatives utilizing HL7 FHIR include:
<bullet> Structured Pharmaceutical Quality/Chemistry,
Manufacturing, and Controls (PQ/CMC): \3\ Aims to standardize
electronic common technical document module 3 data elements,
terminologies, and data structures by adopting HL7 FHIR standard to
enhance the automation of exchange and analyses of PQ/CMC data.
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\3\ See FDA's PQ/CMC web page at <a href="https://www.fda.gov/industry/fda-data-standards-advisory-board/pharmaceutical-qualitychemistry-manufacturing-controls-pqcmcandHL7PQ/CMC">https://www.fda.gov/industry/fda-data-standards-advisory-board/pharmaceutical-qualitychemistry-manufacturing-controls-pqcmcandHL7PQ/CMC</a> project web page at <a href="https://confluence.hl7.org/pages/viewpage.action?pageId=58656205">https://confluence.hl7.org/pages/viewpage.action?pageId=58656205</a>.
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<bullet> Structured Product Labeling (SPL) on FHIR: \4\ Explores
the potential approaches for transitioning from SPL submissions in HL7
version 3 to HL7 FHIR.
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\4\ See HL7 SPL-FHIR project web page at <a href="https://confluence.hl7.org/display/BRR/SPL+V3+to+a+FHIR-based+submission">https://confluence.hl7.org/display/BRR/SPL+V3+to+a+FHIR-based+submission</a>.
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<bullet> CBER Biologics Effectiveness and Safety (BEST) Innovative
Methods (IM) Platform (Ref. 4): A FHIR-based platform (see <a href="https://build.fhir.org/ig/HL7/fhir-icsr-ae-reporting/">https://build.fhir.org/ig/HL7/fhir-icsr-ae-reporting/</a>) which aims to improve
CBER's postmarket surveillance capability through the validation,
detection, and reporting of adverse events from EHRs. BEST IM Platform
piloted two studies to evaluate the quality and timeliness of FHIR for
public health use case (Ref. 5); and to explore using semi-automated
detection of adverse events using interoperable computable phenotypes
(Ref. 6).
<bullet> Application of HL7 FHIR to collect data directly from EHRs
in a clinical trial: \5\ Uses Substitutable Medical Applications
Reusable Technologies on FHIR API to read discrete data from EHRs for a
phase 2 breast cancer clinical trial. In addition, HL7 FHIR is being
used as the exchange standard between health IT and clinical research
systems.
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\5\ See FDA's web page at <a href="https://www.fda.gov/science-research/advancing-regulatory-science/source-data-capture-electronic-health-records-ehrs-using-standardized-clinical-research-data">https://www.fda.gov/science-research/advancing-regulatory-science/source-data-capture-electronic-health-records-ehrs-using-standardized-clinical-research-data</a> and the
Quantum Leap Healthcare Collaborative web page at <a href="https://www.quantumleaphealth.org/partnerships/onesource/">https://www.quantumleaphealth.org/partnerships/onesource/</a>.
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<bullet> Common Data Model Harmonization (Refs. 7, 8): Builds a
data infrastructure for conducting patient-centered outcomes research
using RWD derived from routine clinical settings. This project aims to
establish mappings between various common data models and currently
supported data models, including harmonization with HL7 FHIR US Core.
<bullet> Risk Evaluation and Mitigation Strategies (REMS)
Integration and Interoperability Initiative: <SUP>6 7</SUP> Explores
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the use of standardized APIs, like the open source and freely available
HL7 FHIR APIs, with pharmacy data standards, i.e., National Council for
Prescription Drug Programs SCRIPT, to integrate REMS into prescriber
and pharmacy workflows. The use case ultimately aims to reduce REMS
implementation burden, improve the quality of REMS data for feedback
and evaluation, and optimize safe medication use and health outcomes.
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\6\ See HL7 CodeX REMS Integration and Interoperability
Initiative Use Case project web page at <a href="https://confluence.hl7.org/display/COD/Risk+Evaluation+and+Mitigation+Strategies+%28REMS%29+Integration">https://confluence.hl7.org/display/COD/Risk+Evaluation+and+Mitigation+Strategies+%28REMS%29+Integration</a>.
\7\ See U.S. Medication REMS FHIR IG web page at <a href="https://build.fhir.org/ig/HL7/fhir-medication-rems-ig/">https://build.fhir.org/ig/HL7/fhir-medication-rems-ig/</a>.
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These activities demonstrate FDA's commitment to information
systems modernization as well as openness to using FHIR in general.
More generally, FDA is exploring approaches to modernize
submissions of clinical study data collected from RWD sources to the
Agency using FHIR, while ensuring alignment with other FDA policy
regarding RWD and the work of ASTP/ONC. Given the ubiquity of FHIR-
based data elements generated, exchanged, and used in healthcare
organizations, and considering the overlap between healthcare data and
the information required for clinical research from RWD sources, FDA
seeks input from interested parties regarding the range of challenges
to be addressed when considering the use of FHIR for submission of
clinical study data collected from RWD sources. Additionally, the
Agency is seeking feedback on possible approaches and challenges to
structuring and standardizing study data submissions with RWD sources
using FHIR while aligning with the data interoperability and exchange
standards adopted by HHS through ASTP/ONC. Please use the questions in
section II to frame your comments. Also, please specify which types of
RWD source(s) are pertinent to your comment (for example, EHRs,
insurance claims), if applicable.
II. Request for Comments
FDA is requesting public comment on the questions below. Given the
context of the currently supported data standards and models, technical
guides, terminologies, and exchange formats used for clinical and
nonclinical study data submission to FDA, those used for RWD sources
such as EHRs, and the need to align with ASTP/ONC health IT development
as described above:
1. What challenges do you see for the pharmaceutical industry
regarding the current state of submitting clinical study data collected
from RWD sources to FDA?
2. What opportunities and/or challenges do you see for the
pharmaceutical industry on reaching a future state of clinical study
data submissions collected from RWD sources using HL7 FHIR (e.g.,
business processes, technical considerations)?
3. What are your suggestions on how, from a data standards
perspective, FDA might reach a future state of clinical study data
submissions collected from RWD sources that aligns with ASTP/ONC health
IT goals for HL7 FHIR-based exchange?
4. Does USCDI version 3 provide enough information for collecting
RWD for research purposes? Is there information that USCDI version 3
does not sufficiently address?
5. Under TEFCA, a variety of ``Exchange Purposes'' are authorized.
If ``Research'' was added as an ``Exchange Purpose,'' what role could
TEFCA play with using RWD for clinical research? How could TEFCA
support more efficient collection and exchange of RWD for clinical
research purposes? What challenges might exist with this approach?
III. References
The following references are on display at the Dockets Management
Staff (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Although FDA
verified the website addresses in this document, please note that
websites are subject to change over time.
1. FDA, ``Real-World Evidence,'' web page, September 19, 2024.
Available at: <a href="https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence">https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence</a>.
2. FDA, ``Data Standards for Drug and Biological Product Submissions
Containing Real-World Data,'' guidance for industry, December 2023.
Available at: <a href="https://www.fda.gov/media/153341/download">https://www.fda.gov/media/153341/download</a>.
3. HHS, ``HHS Health IT Alignment Policy,'' web page, September 16,
2024. Available at: <a href="https://www.healthit.gov/topic/hhs-health-it-alignment-policy">https://www.healthit.gov/topic/hhs-health-it-alignment-policy</a>.
4. FDA, ``CBER-CDER Data Standards Program Action Plan,'' August
2024. Available at: <a href="https://www.fda.gov/media/180870/download?attachment">https://www.fda.gov/media/180870/download?attachment</a>.
5. Deady, M., R. Duncan, L.D. Jones, et al. ``Data Quality and
Timeliness Analysis for Post-Vaccination Adverse Event Cases
Reported Through Healthcare Data Exchange to FDA BEST Pilot
Platform,'' Front. Public Health, 12:1379973, 2024. Available at:
<a href="https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1379973/full">https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1379973/full</a>.
6. Deady, M., R. Duncan, M. Sonesen, et al. ``A Computable Phenotype
Algorithm for Post-Vaccination Myocarditis/Pericarditis Detection
Using Real-World Data: Validation Study,'' J Med Internet Res,
26:e54597, doi: 10.2196/54597, 2024. Available at: <a href="https://www.jmir.org/2024/1/e54597">https://www.jmir.org/2024/1/e54597</a>.
7. FDA, National Institutes of Health, and ONC Health IT, ``Common
Data Model Harmonization (CDMH) and Open Standards for Evidence
Generation,'' final report, 2020. Available at: <a href="https://aspe.hhs.gov/sites/default/files/private/pdf/259016/CDMH-Final-Report-14August2020.pdf">https://aspe.hhs.gov/sites/default/files/private/pdf/259016/CDMH-Final-Report-14August2020.pdf</a>.
8. HHS Office of the Assistant Secretary for Planning and
Evaluation, ``Code Map Services for Interoperability of Common Data
Models and Data Standards,'' web page, accessed November 20, 2024.
Available at: <a href="https://aspe.hhs.gov/code-map-services-interoperability-common-data-models-0">https://aspe.hhs.gov/code-map-services-interoperability-common-data-models-0</a>.
Dated: April 16, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-06967 Filed 4-22-25; 8:45 am]
BILLING CODE 4164-01-P
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