Notice2025-22869
Investigator Responsibilities-Safety Reporting for Investigational Drugs and Devices; Guidance for Investigators, Industry, and Institutional Review Boards; Availability
Primary source
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Published
December 16, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or the Agency) is announcing the availability of a final guidance for investigators, industry, and institutional review boards (IRBs) entitled "Investigator Responsibilities--Safety Reporting for Investigational Drugs and Devices." The guidance is intended to help clinical investigators comply with the safety reporting requirements for investigational new drug application (IND) studies and investigational device exemption (IDE) studies. As such, recommendations are provided in this guidance to help investigators identify safety information that needs to be reported to sponsors and IRBs. This guidance finalizes the draft guidance of the same title issued on September 30, 2021.
Full Text
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<title>Federal Register, Volume 90 Issue 239 (Tuesday, December 16, 2025)</title>
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[Federal Register Volume 90, Number 239 (Tuesday, December 16, 2025)]
[Notices]
[Pages 58249-58250]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-22869]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-D-0368]
Investigator Responsibilities--Safety Reporting for
Investigational Drugs and Devices; Guidance for Investigators,
Industry, and Institutional Review Boards; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the availability of a final guidance for investigators,
industry, and institutional review boards (IRBs) entitled
``Investigator Responsibilities--Safety Reporting for Investigational
Drugs and Devices.'' The guidance is intended to help clinical
investigators comply with the safety reporting requirements for
investigational new drug application (IND) studies and investigational
device exemption (IDE) studies. As such, recommendations are provided
in this guidance to help investigators identify safety information that
needs to be reported to sponsors and IRBs. This guidance finalizes the
draft guidance of the same title issued on September 30, 2021.
DATES: The announcement of the guidance is published in the Federal
Register on December 16, 2025.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
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-2021-D-0368 for ``Investigator Responsibilities--Safety Reporting
for Investigational Drugs and Devices.'' Received comments 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.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002; or to the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 800-835-
4709 or 240-402-8010, <a href="/cdn-cgi/l/email-protection#066f6862737572747f28646f696a69616f657546606267286e6e7528616970"><span class="__cf_email__" data-cfemail="cca5a2a8b9bfb8beb5e2aea5a3a0a3aba5afbf8caaa8ade2a4a4bfe2aba3ba">[email protected]</span></a>. Send one self-
addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Juanita Marner, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-2500,
<a href="/cdn-cgi/l/email-protection#c9aaadacbba6a4b989afada8e7a1a1bae7aea6bf"><span class="__cf_email__" data-cfemail="cfacabaabda0a2bf8fa9abaee1a7a7bce1a8a0b9">[email protected]</span></a>; Phillip Kurs, Center for Biologics Evaluation and
Research, Food and Drug Administration, 240-402-7911; or Soma Kalb,
Center for Devices and Radiological Health, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. G318, Silver
Spring, MD 20993-0002, 301-796-6359.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for investigators,
industry, and IRBs entitled ``Investigator Responsibilities--Safety
Reporting for Investigational Drugs and Devices.'' This guidance is
intended to help clinical investigators comply with the safety
reporting requirements for IND studies under 21 CFR 312.64(b) and 21
CFR 312.66 and for IDE studies under 21 CFR 812.150. This guidance also
provides relevant information for persons reporting serious adverse
events (SAEs) for bioavailability (BA) and
[[Page 58250]]
bioequivalence (BE) studies that meet conditions for IND-exemption
under 21 CFR 320.31(d)(3) (IND-exempt BA/BE studies).
In January 2009, FDA issued the final guidance entitled ``Adverse
Event Reporting to IRBs--Improving Human Subject Protection'' (the 2009
procedural final guidance). In the Federal Register of September 29,
2010 (75 FR 59935), FDA published a final rule amending the IND safety
reporting requirements under 21 CFR 312.32 and adding safety reporting
requirements for persons conducting BA and BE studies under Sec.
320.31(d). Subsequently, in December 2012, FDA issued the final
guidance entitled ``Safety Reporting Requirements for INDs and BA/BE
Studies'' (the 2012 final guidance) to help sponsors and investigators
comply with safety reporting requirements for INDs and for IND-exempt
BA/BE studies.
To further improve the overall quality of safety reporting, this
guidance builds upon the concepts in FDA's previously published
guidance documents and provides additional recommendations. This
guidance provides information on safety reporting requirements for
investigators of investigational drugs and investigational devices.
Elsewhere in this issue of the Federal Register, FDA also is
announcing the availability of a guidance entitled ``Sponsor
Responsibilities--Safety Reporting Requirements and Safety Assessment
for IND and Bioavailability/Bioequivalence Studies.'' These two
guidances being announced replace the 2012 final guidance and the 2009
procedural final guidance. Accordingly, FDA is withdrawing the 2012
final guidance and the 2009 procedural final guidance at this time.
This guidance finalizes the draft guidance of the same title issued
on September 30, 2021 (86 FR 54208). FDA considered comments received
on the draft guidance as the guidance was finalized. Changes from the
draft guidance to the final guidance include editorial changes for
clarity, based on public comments.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Investigator Responsibilities--Safety
Reporting for Investigational Drugs and Devices.'' It does not
establish any rights for any person and is not binding on FDA or the
public. You can use an alternative approach if it satisfies the
requirements of the applicable statutes and regulations.
FDA considered the applicability of Executive Order 14192, per
Office of Management and Budget (OMB) guidance in M-25-20, and finds
this action to be deregulatory in nature.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the OMB under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3521). The collections of information in 21 CFR part 50 and part 56
pertaining to the protection of human subjects and IRBs, respectively,
have been approved under OMB control number 0910-0130. The collections
of information in 21 CFR part 312 pertaining to the content and format
of IND applications and the collections of information in Sec. 320.31
pertaining to IND-exempt BA and BE studies have been approved under OMB
control number 0910-0014. The collections of information in 21 CFR part
812 pertaining to IDEs have been approved under OMB control number
0910-0078.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>,
<a href="https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products">https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Lowell M. Zeta,
Acting Deputy Commissioner for Policy, Legislation, and International
Affairs.
[FR Doc. 2025-22869 Filed 12-15-25; 8:45 am]
BILLING CODE 4164-01-P
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