Notice2025-22870
Sponsor Responsibilities-Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies; Guidance for Industry; 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 industry entitled "Sponsor Responsibilities--Safety Reporting Requirements and Safety Assessment for Investigational New Drug Application and Bioavailability/Bioequivalence Studies." The guidance provides recommendations for sponsors and sponsor-investigators to comply with the requirements of investigational new drug application (IND) safety reporting and safety reporting for bioavailability (BA) and bioequivalence (BE) studies. This guidance finalizes the draft guidance of the same title issued on June 28, 2021.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 58250-58252]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-22870]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-2099]
Sponsor Responsibilities--Safety Reporting Requirements and
Safety Assessment for Investigational New Drug Application and
Bioavailability/Bioequivalence Studies; Guidance for Industry;
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 industry entitled
``Sponsor Responsibilities--Safety Reporting Requirements and Safety
Assessment for Investigational New Drug Application and
Bioavailability/Bioequivalence Studies.'' The guidance provides
recommendations for sponsors and sponsor-investigators to comply with
the requirements of investigational new drug application (IND) safety
reporting and safety reporting for bioavailability (BA) and
bioequivalence (BE) studies. This guidance finalizes the draft guidance
of the same title issued on June 28, 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
[[Page 58251]]
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-2020-D-2099 for ``Sponsor Responsibilities--Safety Reporting
Requirements and Safety Assessment for Investigational New Drug
Application and Bioavailability/Bioequivalence Studies.'' 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#6801060c1d1b1c1a11460a010704070f010b1b280e0c0946001b460f071e"><span class="__cf_email__" data-cfemail="8de4e3e9f8fef9fff4a3efe4e2e1e2eae4eefecdebe9eca3e5fea3eae2fb">[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#0e6d6a6b7c61637e4e686a6f2066667d20696178"><span class="__cf_email__" data-cfemail="61020504130e0c11210705004f0909124f060e17">[email protected]</span></a>; or Phillip Kurs, Center for Biologics Evaluation
and Research, Food and Drug Administration, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Sponsor Responsibilities--Safety Reporting Requirements and
Safety Assessment for Investigational New Drug Application and
Bioavailability/Bioequivalence Studies.'' The guidance provides
recommendations to help sponsors and sponsor-investigators comply with
the expedited safety reporting requirements for human drug and
biological products that are being investigated (1) under an IND in
accordance with Sec. 312.32 (21 CFR 312.32) or (2) as part of a BA or
BE study that is exempt from the IND requirements under Sec.
320.31(d)(3) (21 CFR 320.31(d)(3)).
In the Federal Register of September 29, 2010 (75 FR 59935), FDA
published a final rule amending the IND safety reporting requirements
under Sec. 312.32 and adding safety reporting requirements for persons
conducting IND-exempt BA and BE studies under Sec. 320.31. Compliance
with these requirements increases the likelihood that submitted
information will be interpretable and will meaningfully contribute to
the developing safety profile of the investigational drug and improve
the overall quality of safety reporting.
An effective systematic approach by sponsors to safety
surveillance, coupled with focusing on IND safety reports for suspected
adverse reactions that are both serious and unexpected, allows
sponsors, FDA, participating investigators, and institutional review
boards to focus on important safety issues and take actions needed to
minimize the risks of participation in a clinical trial.
Following the publication of the final rule, FDA issued the
guidance for industry and investigators entitled ``Safety Reporting
Requirements for Investigational New Drug Applications and
Bioavailability/Bioequivalence Studies'' (December 2012) (the 2012
final guidance) to help sponsors and investigators comply with safety
reporting requirements for INDs and for BA/BE studies that meet the
conditions for IND exemption under Sec. 320.31(d)(3) (IND-exempt BA/BE
studies). In 2015, FDA issued a draft guidance for industry entitled
``Safety Assessment for Investigational New Drug Application Safety
Reporting'' (December 2015) (the 2015 draft guidance) that primarily
focused on aggregate analysis of serious adverse events for reporting.
In the Federal Register of June 28, 2021 (86 FR 34020), FDA
announced the draft guidance for industry entitled ``Sponsor
Responsibilities--Safety Reporting Requirements and Safety Assessment
for Investigational New Drug Application and Bioavailability/
Bioequivalence Studies'' (the June 2021 draft guidance), which
incorporated content from the 2012 final guidance and the 2015 draft
guidance in terms of sponsors' responsibilities for safety reporting
requirements for INDs and BA/BE studies. The 2015 draft guidance was
withdrawn upon the publication of the June 2021 draft guidance. In
September 2021, FDA issued the draft guidance for industry entitled
``Investigator Responsibilities--Safety Reporting for Investigational
Drugs and Devices'' (the September 2021 draft guidance) to help
clinical investigators comply with the safety reporting requirements of
IND studies and investigational device exemption (IDE)
[[Page 58252]]
studies. The September 2021 draft guidance incorporated content on
investigator reporting under 21 CFR 312.64(b) from the 2012 final
guidance.
In the Federal Register notice announcing the availability of the
June 2021 draft guidance (86 FR 34020), FDA announced that when the
June 2021 draft guidance and the September 2021 draft guidance were
finalized, FDA planned to withdraw the 2012 final guidance because
these guidances would replace the 2012 final guidance.
Elsewhere in this issue of the Federal Register, FDA also has
announced the availability of a final guidance entitled ``Investigator
Responsibilities--Safety Reporting for Investigational Drugs and
Devices.'' Accordingly, FDA is withdrawing the 2012 final guidance at
this time.
This guidance finalizes the June 2021 draft guidance. FDA
considered comments received on the draft guidance as the guidance was
finalized. Changes from the draft to the final guidance include
revisions to the recommended approaches for aggregate analyses to
reduce the need for unblinding to evaluate safety data; additional
considerations for small programs and rare diseases; updated
information for electronic submission of IND safety reports; and
editorial changes for clarity.
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 ``Sponsor Responsibilities--Safety Reporting
Requirements and Safety Assessment for Investigational New Drug
Application and Bioavailability/Bioequivalence Studies.'' 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.
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
OMB under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-
3521). 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 for IND-exempt BA/BE safety reporting
requirements for human drug and biological products have been approved
under OMB control number 0910-0014. The collections of information in
21 CFR part 314 for safety report submissions for applicants with an
approved new drug application and an abbreviated new drug application
have been approved under OMB control number 0910-0001. The collections
of information for submitting Form FDA 3500A and for FDA adverse event
reporting and electronic submissions using the Electronic Submission
Gateway and the Safety Reporting Portal have been approved under OMB
control number 0910-0291. The collections of information in 21 CFR part
11 pertaining to electronic records and signatures have been approved
under OMB control number 0910-0303. The collections of information in
21 CFR part 50 and part 56 pertaining to the protection of human
subjects and institutional review boards, respectively, have been
approved under OMB control number 0910-0130. The collections of
information in 21 CFR 314.80 for submitting periodic adverse drug
experience reports have been approved under OMB control number 0910-
0230. The collections of information in 21 CFR 600.80 for submitting
periodic adverse experience reports for biological products have been
approved under OMB control number 0910-0308.
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/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. 2025-22870 Filed 12-15-25; 8:45 am]
BILLING CODE 4164-01-P
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