Proposed Rule2026-08826
Modification of Certain Terminology in Title 21
Primary source
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Published
May 6, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is issuing a proposed rule to modify certain terminology in Title 21 of the Code of Federal Regulations (CFR) to comply with Executive Order (E.O.) 14168, "Defending Women From Gender Ideology Extremism and Restoring Biological Truth to the Federal Government," issued on January 20, 2025. Specifically, this proposed rule, if finalized, will remove the term "gender" wherever it appears and either replace it with the term "sex," or delete reference to gender, as applicable, along with other editorial changes to improve readability.
Full Text
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<title>Federal Register, Volume 91 Issue 87 (Wednesday, May 6, 2026)</title>
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[Federal Register Volume 91, Number 87 (Wednesday, May 6, 2026)]
[Proposed Rules]
[Pages 24380-24387]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-08826]
[[Page 24380]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 10, 56, 106, 201, 251, 310, 312, 314, 329, 600, 803,
862, 866, 870, 882, 1114
[Docket No. FDA-2026-N-2886]
RIN 0910-AJ26
Modification of Certain Terminology in Title 21
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing a proposed rule to modify certain terminology in Title 21 of
the Code of Federal Regulations (CFR) to comply with Executive Order
(E.O.) 14168, ``Defending Women From Gender Ideology Extremism and
Restoring Biological Truth to the Federal Government,'' issued on
January 20, 2025. Specifically, this proposed rule, if finalized, will
remove the term ``gender'' wherever it appears and either replace it
with the term ``sex,'' or delete reference to gender, as applicable,
along with other editorial changes to improve readability.
DATES: Submit either electronic or written comments on the proposed
rule by July 6, 2026.
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 July 6, 2026. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely considered timely if they are postmarked or the
delivery service acceptance receipt is 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-2026-N-2886 for ``Modification of Certain Terminology in Title
21.'' 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 Division of Dockets Management. 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="http://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf">http://www.gpo.gov/fdsys/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: Swati Kabaria, Office of Policy,
Office of Policy, Legislation, and International Affairs, Office of the
Commissioner, Food and Drug Administration, 10903 New Hampshire Ave.,
Silver Spring, MD 20993, 1-888-463-6332.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations
III. Background
A. Need for the Regulation
B. FDA's Current Regulatory Framework
IV. Legal Authority
V. Description of the Proposed Rule
VI. Proposed Effective Date
VII. Economic Analysis of Impacts
VIII. Paperwork Reduction Act of 1995
IX. Analysis of Environmental Impact
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments
I. Executive Summary
A. Purpose of the Proposed Rule
FDA is proposing to amend certain terminology in Title 21 of the
CFR to remove the term ``gender'' wherever it appears, to either
replace it with the term ``sex,'' or delete reference to gender, as
applicable, and make other editorial changes to the relevant sections
for readability. FDA is taking this action to comply with E.O. 14168,
``Defending Women From Gender Ideology Extremism and Restoring
[[Page 24381]]
Biological Truth to the Federal Government.'' \1\
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\1\ <a href="https://www.federalregister.gov/documents/2025/01/30/2025-02090/defending-women-from-gender-ideology-extremism-and-restoring-biological-truth-to-the-federal">https://www.federalregister.gov/documents/2025/01/30/2025-02090/defending-women-from-gender-ideology-extremism-and-restoring-biological-truth-to-the-federal</a>.
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B. Summary of the Major Provisions of the Proposed Rule
The proposed rule would remove the term ``gender'' wherever it
appears, to either replace it with the term ``sex,'' or delete
reference to gender, as applicable, and make other editorial changes
for readability, in the following regulations in Title 21 of the CFR:
21 CFR 10.65, 56.107, 106.121, 201.57, 251.18, 310.305, 312.33, 312.42,
314.50, 314.80, 329.100, 600.80, 803.32, 803.42, 803.52, 862.1840,
866.3215, 866.5950, 870.1415, 870.2200, 870.2210, 870.2220, 870.5600,
882.1455, 882.1471, 1114.3, and 1114.41.
C. Legal Authority
FDA proposes to issue this rule under the following authorities:
The Federal Food, Drug, and Cosmetic Act (FD&C Act) at 21 U.S.C. 321 et
seq. and specifically, sections 321-397; the Public Health Service (PHS
Act) at 42 U.S.C. 201, 216, 241, 242(a), 262, 263a, 263b, 264; 15
U.S.C. 1451-1461; 5 U.S.C. 551-558, 701-706; 21 U.S.C. 141-149, 467f,
679, 821, 1034; 28 U.S.C. 2112; and section 111 of the Consolidated
Appropriations Act, 2022 (Pub. L. 117-103), 136 Stat. 49 at 789. FDA
also has general authority to issue regulations for the efficient
enforcement of the FD&C Act and the PHS Act under section 701 of the
FD&C Act (21 U.S.C. 371) and section 351(j) of the PHS Act.
D. Costs and Benefits
FDA is proposing to remove the term ``gender'' wherever it appears,
and either replace it with the term ``sex,'' or delete reference to
gender, as applicable, and make other editorial changes for
readability. This proposed rule reflects editorial changes that affect
FDA and does not impact industry practices. Consequently, we do not
anticipate any measurable change in industry resulting from this
proposed rule. We also expect the economic impact on FDA to be minimal.
This proposed rule will produce no quantifiable savings, costs, or
transfers. We do not expect any loss of public health benefits as a
result of this rule. We estimate that the annualized benefits over 10
years would be $0 at both 3 and 7 percent discount rate. The annualized
costs would also be $0 at both 3 and 7 percent discount rate.
This proposed rule, if finalized, is not expected to be an
Executive Order 14192 regulatory action. We estimate that this proposed
rule would generate $0 in net cost savings.
II--Table of Abbreviations/Commonly Used Acronyms in This Document
------------------------------------------------------------------------
Abbreviation/ acronym What it means
------------------------------------------------------------------------
CFR....................................... Code of Federal Regulations.
E.O....................................... Executive Order.
FD&C Act.................................. Federal Food, Drug, and
Cosmetic Act.
FDA or Agency............................. Food and Drug
Administration.
IDE....................................... Investigational Device
Exemption.
IND....................................... Investigational New Drug.
NDA....................................... New Drug Application.
OMB....................................... Office of Management and
Budget.
PHS Act................................... Public Health Service Act.
------------------------------------------------------------------------
III. Background
A. Need for the Regulation
On January 20, 2025, the President issued E.O. 14168, ``Defending
Women From Gender Ideology Extremism and Restoring Biological Truth to
the Federal Government,'' which, among other things, requires executive
agencies to use the term ``sex'' and not ``gender'' when administering
or enforcing sex-based distinctions, in all applicable Federal policies
and documents.
Accordingly, this proposed rule would, if finalized, amend certain
terminology in FDA regulations, specifically by removing the word
``gender'' wherever it appears, to either replace it with the term
``sex,'' or delete reference to gender, as applicable, and make other
appropriate editorial changes for readability.
B. FDA's Current Regulatory Framework
The terms ``gender'' and ``sex'' appear in various contexts in FDA
regulations, including in requirements related to Institutional Review
Board (IRB) membership (see 21 CFR 56.107), records and reporting
requirements for product applications and approvals (see, e.g., 21 CFR
312.42, 314.50, 314.80, 600.80, 803.32), and device classification
regulations (see, e.g., 21 CFR 862.1840, 866.3215, 866.5950). Section
2(a) of E.O. 14168 defines ``sex'' as referring to an individual's
immutable biological classification as either male or female. Section
3(c) of E.O. 14168 requires, among other things, that ``[w]hen
administering or enforcing sex-based distinctions, every agency and all
Federal employees acting in an official capacity on behalf of their
agency shall use the term ``sex'' and not ``gender'' in all applicable
Federal policies and documents.'' After reviewing them, FDA is
modifying regulations to remove the term ``gender'' wherever it
appears, to either replace it with the term ``sex,'' or delete
reference to gender, as applicable.
IV. Legal Authority
FDA is proposing this rule under the authority granted to it by the
FD&C Act (21 U.S.C. 301 et seq.),the PHS Act (42 U.S.C. 201 et seq.),
15 U.S.C. 1451-1461; 5 U.S.C. 551-558, 701-706; 21 U.S.C. 141-149,
467f, 679, 821, 1034; 28 U.S.C. 2112; and section 111 of the
Consolidated Appropriations Act, 2022. The statutory authorities
supporting this rulemaking are those authorizing the regulations which
are to be amended. Specifically, FDA is proposing this rule under the
following statutes and public laws: 21 U.S.C. 321-397; 42 U.S.C. 201,
216, 241, 242(a), 262, 263a, 263b, 264; 15 U.S.C. 1451-1461; 5 U.S.C.
551-558, 701-706; 21 U.S.C. 141-149, 467f, 679, 821, 1034; 28 U.S.C.
2112; and section 111 of the Consolidated Appropriations Act of 2022.
By delegation from the Secretary of the Department of Health and Human
Services, FDA is authorized to issue regulations for the efficient
enforcement of the FD&C Act (21 U.S.C. 371) and section 351(j) of the
PHS Act (42 U.S.C. 262(j)). Any final rule upon which this proposal is
based would help with the efficient enforcement of provisions relating
to the following: (1) IRBs; (2) infant formula; (3) human and animal
drugs, biological products, and medical devices; (4) drug, biological
product, and device labeling and reporting; (5) drug importation; and
(6) premarket tobacco product applications.
V. Description of the Proposed Rule
We propose to amend regulations concerning IRBs; infant formula;
human and animal drugs, biological products, and medical devices; drug,
biological product, and device labeling and reporting; drug
importation; and premarket tobacco product applications by removing the
term ``gender'' wherever it appears, to either replace it with the term
``sex,'' or delete reference to gender, as applicable, and make other
appropriate editorial changes for readability in Title 21 of the CFR:
[[Page 24382]]
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Chapter/subchapter Heading
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1. Sec. 10.65(d)(3)............. Meetings and correspondence.
2. Sec. 56.107(a)............... IRB membership.
3. Sec. 56.107(b)............... IRB membership.
4. Sec. 106.121(a)(2)........... Quality factor assurances for infant
formulas.
5. Sec. 201.57(c)(13)(i)(C)..... Specific requirements on content and
format of labeling for human
prescription drug and biological
products described in Sec.
201.56(b)(1).
6. Sec. 251.18(d)(7)(i)(C)...... Post-importation requirements.
7. Sec. 310.305(d)(1)(iii)...... Records and reports concerning
adverse drug experiences on
marketed prescription drugs for
human use without approved new drug
applications.
8. Sec. 312.33 (a)(2)........... Annual reports.
9. Sec. 312.42(b)(1)(v)......... Clinical holds and requests for
modification.
10. Sec. 312.42(b)(1)(v)(A)..... Clinical holds and requests for
modification.
11. Sec. 312.42(b)(1)(v)(B)..... Clinical holds and requests for
modification.
12. Sec. 314.50(d)(5)(v)........ Content and format of an NDA.
13. Sec. 314.50(d)(5)(vi)....... Content and format of an NDA.
14. Sec. 314.80(f)(1)(iii)...... Postmarketing reporting of adverse
drug experiences.
15. Sec. 329.100(b)(1)(iii)..... Postmarketing reporting of adverse
drug events under section 760 of
the Federal Food, Drug, and
Cosmetic Act.
16. Sec. 600.80(f)(1)(iii)...... Postmarketing reporting of adverse
experiences.
17. Sec. 600.80(g)(1)(iii)...... Postmarketing reporting of adverse
experiences.
18. Sec. 803.32(a)(3)........... If I am a user facility, what
information must I submit in my
individual adverse event reports?
19. Sec. 803.42 (a)(3).......... If I am an importer, what
information must I submit in my
individual adverse event reports?
20. Sec. 803.52(a)(3)........... If I am a manufacturer, what
information must I submit in my
individual adverse event reports?
21. Sec. 862.1840(b)(3)......... Total 25-hydroxyvitamin D mass
spectrometry test system.
22. Sec. 866.3215(b)(5)......... Device to detect and measure non-
microbial analyte(s) in human
clinical specimens to aid in
assessment of patients with
suspected sepsis.
23. Sec. 866.5950(b)(3)(ii)(B).. Genetic health risk assessment
system.
24. Sec. Genetic health risk assessment
866.5950(b)(3)(iii)(J)(1)(viii). system.
25. Sec. 870.1415(b)(6)(v)...... Coronary vascular physiologic
simulation software device.
26. Sec. 870.2200(b)(5)(vii).... Adjunctive cardiovascular status
indicator.
27. Sec. 870.2210(b)(5)(viii)... Adjunctive predictive cardiovascular
indicator.
28. Sec. 870.2220(b)(5)(v)...... Adjunctive hemodynamic indicator
with decision point.
29. Sec. 870.5600(b)(5)(ix)..... Adjunctive open loop fluid therapy
recommender.
30. Sec. 882.1455(b)(6)(ii)(E).. Traumatic brain injury eye movement
assessment aid.
31. Sec. 882.1471(b)(3)(i)(D)(5) Computerized cognitive assessment
aid for concussion.
32. Sec. 1114.3................. Definitions.
33. Sec. 1114.41(a)(1)(vi)(C)... Reporting requirements.
34. Sec. 1114.41(a)(1)(xvi)..... Reporting requirements.
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VI. Proposed Effective Date
We propose that any final rule resulting from this rulemaking would
become effective 30 days after the date of the final rule's publication
in the Federal Register.
VII. Economic Analysis of Impacts
We have examined the impacts of the proposed rule under E.O. 12866,
E.O. 13563, E.O. 14192, the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4).
Executive Orders 12866 and 13563 direct us to assess all benefits
and costs of available regulatory alternatives and, when regulation is
necessary, to select regulatory approaches that maximize net benefits.
Rules are economically significant under E.O. 12866 if they have an
annual effect on the economy of $100 million or more; or adversely
affect in a material way the economy, a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local, or tribal governments or communities. The
Office of Information and Regulatory Affairs (OIRA) has determined that
this proposed rule is not a significant regulatory action under E.O.
12866.
E.O. 14192 requires that any new incremental costs associated with
certain significant regulatory actions ``shall, to the extent permitted
by law, be offset by the elimination of existing costs associated with
at least 10 prior regulations.'' This proposed rule, if finalized as
proposed, is not expected to be an E.O. 14192 regulatory action because
this rule is not significant under E.O. 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because the proposed rule reflects editorial changes and does
not add any new regulatory burden on the industry, we propose to
certify that the proposed rule will not have a significant economic
impact on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $193 million, using the most current (2025) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount.
FDA is proposing to remove the term ``gender'' wherever it appears,
and either replace it with the term ``sex,'' or delete reference to
gender, as applicable, and make other editorial changes for
readability. This proposed rule reflects editorial changes that affect
FDA and does not impact industry practices. Consequently, we do not
anticipate any measurable change in industry resulting from this
proposed rule. We also expect the economic impact on FDA to be minimal.
This proposed rule will produce no quantifiable savings, costs, or
transfers. We do not expect any loss
[[Page 24383]]
of public health benefits as a result of this rule.
Table 1 summarizes the estimated benefits and costs of the proposed
rule. We estimate that the annualized benefits over 10 years would be
$0 at both 3 and 7 percent discount rate. The annualized costs would
also be $0 at both 3 and 7 percent discount rate. We request comments
on our estimates of benefits, costs, and transfers of this proposed
rule.
Table 1--Summary of Benefits, Costs, and Distributional Effects of the Proposed Rule
[Millions of 2024 dollars]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
Primary Low High ------------------------------------
Category estimate estimate estimate Year Discount Period Notes
dollars rate (%) covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized Monetized ($millions/year)....................... $0 $0 $0 .......... 7 ..........
3
Annualized Quantified....................................... .......... .......... .......... .......... 7 ..........
3
---------------------------------------------------------------------------------------
Qualitative.................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
Annualized Monetized ($millions/year)....................... 0 0 0 .......... 7 ..........
3
---------------------------------------------------------------------------------------
Annualized Quantified....................................... .......... .......... .......... .......... 7 ..........
3
---------------------------------------------------------------------------------------
Qualitative.................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
Federal Annualized Monetized ($millions/year)............... .......... .......... .......... .......... 7 ..........
3
---------------------------------------------------------------------------------------
From:
To:
---------------------------------------------------------------------------------------
Other Annualized Monetized ($millions/year)................. .......... .......... .......... .......... 7 ..........
3
---------------------------------------------------------------------------------------
From:
To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
State, Local or Tribal Government: none.............................................................................................................
Small Business: none................................................................................................................................
Wages: none.........................................................................................................................................
Growth: none........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
In line with E.O. 14192, in Table 2 we estimate present and
annualized values of costs, cost savings, and net costs over a
perpetual time horizon. This proposed rule, if finalized as proposed,
is not expected to be an E.O. 14192 regulatory action. We estimate that
this proposed rule would generate $0 in net cost savings.
Table 2--Executive Order 14192 Summary Table
[Millions of 2024 dollars, discounted over a perpetual time horizon relative to year 2024 at a 7 percent
discount rate]
----------------------------------------------------------------------------------------------------------------
Primary estimate Low estimate High estimate
----------------------------------------------------------------------------------------------------------------
Present Value of Costs...................................... $0 $0 $0
Present Value of Cost Savings............................... 0 0 0
Present Value of Net Costs.................................. 0 0 0
Annualized Costs............................................ 0 0 0
Annualized Cost Savings..................................... 0 0 0
Annualized Net Costs........................................ 0 0 0
----------------------------------------------------------------------------------------------------------------
VIII. Paperwork Reduction Act of 1995
FDA tentatively concludes that this proposed rule contains no
collection of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 (44
U.S.C. 3501-3521) is not required.
IX. Analysis of Environmental Impact
We have determined under 21 CFR 25.30(h) that this action is of a
type that does not normally have a significant effect on the human
environment. Therefore, neither an environmental assessment nor an
environmental impact statement is required.
X. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in E.O. 13132. We have determined that this
proposed rule does not contain policies that have substantial direct
effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the rule does not contain policies that have
federalism implications as defined in the E.O. and,
[[Page 24384]]
consequently, a federalism summary impact statement is not required.
XI. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in E.O. 13175. We have tentatively determined that
the rule does not contain policies that would have a substantial direct
effect on one or more Indian Tribes, on the relationship between the
Federal Government and Indian Tribes, or on the distribution of power
and responsibilities between the Federal Government and Indian Tribes.
The Agency solicits comments from tribal officials on any potential
impact on Indian Tribes from this proposed action.
List of Subjects
21 CFR Part 10
Administrative practice and procedure; News media.
21 CFR Part 56
Human research subjects; Reporting and recordkeeping requirements;
Safety.
21 CFR Part 106
Food grades and standards; Infants and children; Nutrition;
Reporting and Recordkeeping Requirements.
21 CFR Part 201
Drugs; Labeling; Reporting and recordkeeping requirements.
21 CFR Part 251
Exports; Labeling; Packaging and containers; Prescription drugs;
Reporting and recordkeeping requirements.
21 CFR Part 310
Administrative practice and procedure; Drugs; Labeling; Medical
devices; Reporting and recordkeeping requirements.
21 CFR Part 312
Drugs; Exports; Imports; Investigations; Labeling; Medical
research; Reporting and recordkeeping requirements.
21 CFR Part 314
Administrative practice and procedure; Confidential business
information; Drugs; Reporting and recordkeeping requirements.
21 CFR Part 329
Alcohol and alcoholic beverages; Over-the-counter drugs; Reporting
and recordkeeping requirements.
21 CFR Part 600
Biologics; Reporting and recordkeeping requirements.
21 CFR Part 803
Imports; Medical devices; Reporting and recordkeeping requirements.
21 CFR Part 862
Medical devices.
21 CFR Part 866
Biologics; Laboratories; Medical devices.
21 CFR Part 870
Medical devices.
21 CFR Part 882
Medical devices.
21 CFR Part 1114
Administrative practice and procedure; Cigars and cigarettes;
Smoking; Tobacco.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, we propose
that 21 CFR parts 10, 56, 106, 201, 251, 310, 312, 314, 329, 600, 803,
862, 866, 870, 882, and 1114 be amended as follows:
PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURE
0
1. The authority citation for part 10 continues to read as follows:
Authority: 5 U.S.C. 551-558, 701-706; 15 U.S 1451-1461; 21
U.S.C. 141-149, 321-397, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42
U.S.C. 201, 262, 263b, 264.
0
2. Revise Sec. 10.65 to read as follows:
Sec. 10.65 Meetings and correspondence.
* * *
(d) * * *
(3) An agency representative may not knowingly participate in a
meeting that is closed on the basis of sex, race, or religion.
* * *
PART 56--INSTITUTIONAL REVIEW BOARDS
0
1. The authority citation for part 56 continues to read as follows:
Authority: 21 U.S.C. 321, 343, 346, 346a, 350a, 351, 352, 353,
355, 360, 360-360-f, 360h, 360i, 360j, 360hh-360ss, 371, 379e, 381;
42 U.S.C 216, 241, 262.
0
2. Revise Sec. 56.107 to read as follows:
Sec. 56.107 IRB membership.
(a) Each IRB shall have at least five members, with varying
backgrounds to promote complete and adequate review of research
activities commonly conducted by the institution. The IRB shall be
sufficiently qualified through the experience and expertise of its
members, and the diversity of the members, including consideration of
race, sex, cultural backgrounds, and sensitivity to such issues as
community attitudes, to promote respect for its advice and counsel in
safeguarding the rights and welfare of human subjects. In addition to
possessing the professional competence necessary to review the specific
research activities, the IRB shall be able to ascertain the
acceptability of proposed research in terms of institutional
commitments and regulations, applicable law, and standards of
professional conduct and practice. * * * The IRB shall therefore
include persons knowledgeable in these areas. If an IRB regularly
reviews research that involves a vulnerable category of subjects, such
as children, prisoners, pregnant women, or handicapped or mentally
disabled persons, consideration shall be given to the inclusion of one
or more individuals who are knowledgeable about and experienced in
working with those subjects.
* * * * *
(b) Every nondiscriminatory effort will be made to ensure that no
IRB consists entirely of men or entirely of women, including the
institution's consideration of qualified persons of both sexes, so long
as no selection is made to the IRB on the basis of sex. No IRB may
consist entirely of members of one profession.
* * * * *
PART 106--INFANT FORMULA REQUIREMENTS PERTAINING TO CURRENT GOOD
MANUFACTURING PRACTICE, QUALITY CONTROL PROCEDURES, QUALITY
FACTORS, RECORDS AND REPORTS, AND NOTIFICATIONS
0
1. The authority citation for part 106 continues to read as follows:
Authority: 21 U.S.C. 321, 342, 350a, 371.
0
2. Revise Sec. 106.121 to read as follows:
Sec. 106.121 Quality factor assurances for infant formulas.
(a) * * *
(2) Records that contain the information required by Sec.
106.96(b) to be collected during the study for each infant enrolled in
the study. The records shall be identified by subject number, age,
feeding group, sex, and study day of collection.
* * * * *
[[Page 24385]]
PART 201--LABELING
0
1. The authority citation for part 201 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 343, 351, 352, 353, 355, 358,
360, 360b, 360ccc, 360ccc-1, 360ee, 360gg-360ss, 371, 374, 379e, 42
U.S.C. 216, 241, 262, 264.
0
2. Revise Sec. 201.57 to read as follows:
Sec. 201.57 Specific requirements on content and format of labeling
for human prescription drug and biological products described in Sec.
201.56(b)(1).
* * * * *
(c) * * *
(13) * * *
(i) * * *
(C) 12.3 Pharmacokinetics. This subsection must describe the
clinically significant pharmacokinetics of a drug or active
metabolites, (i.e., pertinent absorption, distribution, metabolism, and
excretion parameters). Information regarding bioavailability, the
effect of food, minimum concentration (C<INF>min</INF>), maximum
concentration (C<INF>max</INF>), time to maximum concentration
(T<INF>max</INF>), area under the curve (AUC), pertinent half-lives
(t<INF>1/2</INF>), time to reach steady state, extent of accumulation,
route(s) of elimination, clearance (renal, hepatic, total), mechanisms
of clearance (e.g., specific enzyme systems), drug/drug and drug/food
(e.g., dietary supplements, grapefruit juice) pharmacokinetic
interactions (including inhibition, induction, and genetic
characteristics), and volume of distribution (V<INF>d</INF>) must be
presented if clinically significant. Information regarding nonlinearity
in pharmacokinetic parameters, changes in pharmacokinetics over time,
and binding (plasma protein, erythrocyte) parameters must also be
presented if clinically significant. This section must also include the
results of pharmacokinetic studies (e.g., of metabolism or interaction)
that establish the absence of an effect, including pertinent human
studies and in vitro data. Dosing recommendations based on clinically
significant factors that change the product's pharmacokinetics (e.g.,
age, sex, race, hepatic or renal dysfunction, concomitant therapy) that
appear in other sections (e.g., ``Warnings and Precautions,'' ``Dosage
and Administration,'' or ``Use in Specific Populations'') must not be
repeated in this subsection, but the location of such recommendations
must be referenced.
* * * * *
PART 251--SECTION 804 IMPORTATION PROGRAM
0
1. The authority citation for part 251 continues to read as follows:
Authority: 21 U.S.C. 351, 352, 353, 355, 360, 360b-f, 360ee-
1,371, 374, 381, 384.
0
2. Revise Sec. 251.18 to read as follows:
Sec. 251.18 Post-importation requirements.
* * *
(d) * * *
(7) * * *
(i) * * *
(C) Patient sex; and
* * *
PART 310--NEW DRUGS
0
1. The authority citation for part 310 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f,
360j, 360hh-360ss, 361(a), 371, 374, 375, 379e, 379k-1; 42 U.S.C.
216, 241, 242(a), 262.
0
2. Revise Sec. 310.305 to read as follows:
Sec. 310.305 Records and reports concerning adverse drug experiences
on marketed prescription drugs for human use without approved new drug
applications.
* * * * *
(d) * * *
(1) * * *
(iii) Patient sex; and
* * * * *
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
0
1. The authority citation for part 312 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360bbb, 371;
42 U.S.C. 262.
0
2. Revise Sec. 312.33 to read as follows:
Sec. 312.33 Annual reports.
(a) * * *
(2) The total number of subjects initially planned for inclusion in
the study; the number entered into the study to date, tabulated by age
group, sex, and race; the number whose participation in the study was
completed as planned; and the number who dropped out of the study for
any reason
* * * * *
0
3. Revise Sec. 312.42 to read as follows:
Sec. 312.42 Clinical holds and requests for modification.
* * * * *
(b) * * *
(1) * * *
(v) The IND is for the study of an investigational drug intended to
treat a life-threatening disease or condition that affects both sexes,
and men or women with reproductive potential who have the disease or
condition being studied are excluded from eligibility because of a risk
or potential risk from use of the investigational drug of reproductive
toxicity (i.e., affecting reproductive organs) or developmental
toxicity (i.e., affecting potential offspring). The phrase ``women with
reproductive potential'' does not include pregnant women. For purposes
of this paragraph, ``life-threatening illnesses or diseases'' are
defined as ``diseases or conditions where the likelihood of death is
high unless the course of the disease is interrupted.'' The clinical
hold would not apply under this paragraph to clinical studies
conducted:
(A) Under special circumstances, such as studies pertinent only to
one sex (e.g., studies evaluating the excretion of a drug in semen or
the effects on menstrual function);
(B) Only in men or women, as long as a study that does not exclude
members of the other sex with reproductive potential is being conducted
concurrently, has been conducted, or will take place within a
reasonable time agreed upon by the agency; or
* * * * *
PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG
0
1. The authority citation for part 314 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 355a, 355f,
356, 356a, 356b, 356c, 356e, 360cc, 371, 374, 379e, 379k-1.
0
2. Revise Sec. 314.50 to read as follows:
Sec. 314.50 Content and format of an NDA.
* * * * *
(d) * * *
(5) * * *
(v) An integrated summary of the data demonstrating substantial
evidence of effectiveness for the claimed indications. Evidence is also
required to support the dosage and administration section of the
labeling, including support for the dosage and dose interval
recommended. The effectiveness data must be presented by sex, age, and
racial subgroups and must identify any modifications of dose or dose
interval needed for specific subgroups. Effectiveness data from other
subgroups of the population of patients treated, when appropriate, such
as patients with renal failure or patients with different levels of
severity of the disease, also must be presented.
(vi) * * *
(a) The applicant must submit an integrated summary of all
available information about the safety of the drug product, including
pertinent animal data, demonstrated or potential adverse effects of the
drug, clinically significant drug/drug interactions, and other safety
considerations, such as data from epidemiological studies of related
drugs.
[[Page 24386]]
The safety data must be presented by sex, age, and racial subgroups.
When appropriate, safety data from other subgroups of the population of
patients treated also must be presented, such as for patients with
renal failure or patients with different levels of severity of the
disease. A description of any statistical analyses performed in
analyzing safety data should also be included, unless already included
under paragraph (d)(5)(ii) of this section.
* * *
0
3. Revise Sec. 314.80 to read as follows:
Sec. 314.80 Postmarketing reporting of adverse drug experiences.
* * * * *
(f) * * *
(1) * * *
(iii) Patient sex; and
* * * * *
PART 329--NONPRESCRIPTION HUMAN DRUG PRODUCTS SUBJECT TO SECTION
760 OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT
0
1. The authority citation for part 329 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371, 379aa.
0
2. Revise Sec. 329.100 to read as follows:
Sec. 329.100 Postmarketing reporting of adverse drug events under
section 760 of the Federal Food, Drug, and Cosmetic Act.
* * * * *
(b) * * *
(1) * * *
(iii) Patient sex; and
* * * * *
PART 600--BIOLOGICAL PRODUCTS: GENERAL
0
1. The authority citation for part 600 continues to read as follows:
Authority: 21 U.S.C. 321, 351, 353, 355, 356C, 356e, 360, 360i,
371, 374, 379k-1; 42 U.S.C. 216, 262, 263, 263a, 264.
0
2. Revise Sec. 600.80 to read as follows:
Sec. 600.80 Postmarketing reporting of adverse experiences.
* * * * *
(f) * * *
(1) * * *
(iii) Patient sex; and
* * * * *
(g) * * *
(1) * * *
(iii) Patient sex; and
* * * * *
PART 803--MEDICAL DEVICE REPORTING
0
1. The authority citation for part 803 continues to read as follows:
Authority: 21 U.S.C. 352, 360, 360i, 0360j, 371, 374.
0
2. Revise Sec. 803.32 to read as follows:
Sec. 803.32 If I am a user facility, what information must I submit
in my individual adverse event reports?
* * * * *
(a) * * *
(3) Patient sex; and
* * * * *
0
3. Revise Sec. 803.42 to read as follows:
Sec. 803.42 If I am an importer, what information must I submit in my
individual adverse event reports?
* * * * *
(a) * * *
(3) Patient sex; and
* * * * *
0
4. Revise Sec. 803.52 to read as follows:
Sec. 803.52 If I am a manufacturer, what information must I submit in
my individual adverse event reports?
* * * * *
(a) * * *
(3) Patient sex; and
* * * * *
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for part 862 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Revise Sec. 862.1840 to read as follows:
Sec. 862.1840 Total 25-hydroxyvitamin D mass spectrometry test
system.
* * * * *
(b) * * *
(3) The 21 CFR 809.10(b) compliant labeling must be supported by a
reference range study representative of the performance of the device.
The study must be conducted using samples collected from apparently
healthy male and female adults at least 21 years of age and older from
at least 3 distinct climatic regions within the United States in
different weather seasons. Demographic characteristics (e.g., ethnic,
racial, and sex distribution) of this study population must be
representative of the U.S. population demographics.
* * * * *
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
1. The authority citation for part 866 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Revise Sec. 866.3215 to read as follows:
Sec. 866.3215 Device to detect and measure non-microbial analyte(s)
in human clinical specimens to aid in assessment of patients with
suspected sepsis.
* * * * *
(b) * * *
(5) Premarket notification submissions must include evaluation of
the level of the non-microbial analyte in asymptomatic patients with
demographic characteristics (e.g., age, racial, ethnic, and sex
distribution) similar to the Intended Use population.
* * * * *
0
3. Revise Sec. 866.5950 to read as follows:
Sec. 866.5950 Genetic health risk assessment system.
* * * * *
(b) * * *
(3) * * *
(ii) * * *
(B) Clear context for the user to understand the context in which
the cited clinical performance data support the risk reported. This
includes, but is not limited to, any risks that are influenced by
ethnicity, age, sex, environment, and lifestyle choices.
* * * * *
(iii) * * *
(J) * * *
(1) * * *
(viii) Information must be reported on the Technical Positive
Predictive Value (TPPV) related to the analytical (technical)
performance of the device for genotypes in each relevant subpopulation
(e.g., ethnicity, sex, age, geographical location, etc.). TPPV is the
percentage of individuals with the genotype truly present among
individuals whose test reports indicate that this genotype is present.
The TPPV depends on the accuracy measures of percent agreements and on
the frequency of the genotypes in the subpopulation being studied. The
f(DD) is the frequency of DD and f(Dd) is the frequency of Dd in the
subpopulation being studied; TPPV must be calculated as described in
paragraphs (b)(3)(iii)(J)(1)(ix) through (xi) of this section.
* * * * *
PART 870--CARDIOVASCULAR DEVICES
0
1. The authority citation for part 870 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c 360e, 360j, 360l, 371.
0
2. Revise Sec. 870.1415 to read as follows:
Sec. 870.1415 Coronary vascular physiologic simulation software
device.
* * * * *
[[Page 24387]]
(b) * * *
(6) * * *
(v) A detailed description of the patients studied in the clinical
validation (e.g., age, sex, race or ethnicity, clinical stability,
current treatment regimen) as well as procedural details of the
clinical study (e.g., scanner representation, calcium scores, use of
beta-blockers or nitrates); and
* * * * *
0
3. Revise Sec. 870.2200 to read as follows:
Sec. 870.2200 Adjunctive cardiovascular status indicator.
* * * * *
(b) * * *
(5) * * *
(vii) A detailed description of the patients studied in the
clinical validation (e.g., age, sex, race/ethnicity, clinical
stability) as well as procedural details of the clinical study.
0
4. Revise Sec. 870.2210 to read as follows:
Sec. 870.2210 Adjunctive predictive cardiovascular indicator.
* * * * *
(b) * * *
(5) * * *
(viii) Relevant characteristics of the patients studied in the
clinical validation (including age, sex, race or ethnicity, and patient
condition) and a summary of validation results.
0
5. Revise Sec. 870.2220 to read as follows:
Sec. 870.2220 Adjunctive hemodynamic indicator with decision point.
* * * * *
(b) * * *
(5) * * *
(v) A summary of the clinical validation data, including details of
the patient population studied (e.g., age, sex, race/ethnicity),
clinical study protocols, and device performance with confidence
intervals for all intended use populations.
0
6. Revise Sec. 870.5600 to read as follows:
Sec. 870.5600 Adjunctive open loop fluid therapy recommender.
* * * * *
(b) * * *
(5) * * *
(ix) Relevant characteristics of the patients studied in the
clinical validation (such as age, sex, race or ethnicity, and patient
condition) and a summary of validation results; and
* * * * *
PART 882--NEUROLOGIC DEVICES
0
1. The authority citation for part 882 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Revise Sec. 882.1455 to read as follows:
Sec. 882.1455 Traumatic brain injury eye movement assessment aid.
* * * * *
(b) * * *
(6) * * *
(ii) * * *
(E) Any adjustments for age and sex.
* * * * *
0
3. Revise Sec. 882.1471 to read as follows:
Sec. 882.1471 Computerized cognitive assessment aid for concussion.
* * * * *
(b) * * *
(3) * * *
(i) * * *
(D) * * *
(5) Whether or not the normative database was adjusted due to
differences in age and sex.
* * * * *
PART 1114--PREMARKET TOBACCO PRODUCT APPLICATIONS
0
1. The authority citation for part 1114 continues to read as follows:
Authority: 21 U.S.C. 371, 374, 387a, 387i, 387j; Public Law 117-
103, 136 Stat. 49.
0
2. Revise Sec. 1114.3 to read as follows:
Sec. 1114.3 Definitions.
* * * * *
Vulnerable populations means groups that are susceptible to tobacco
product risk and harm due to disproportionate rates of tobacco product
initiation, use, burden of tobacco-related diseases, or decreased
cessation. Vulnerable populations can be based on criteria such as age
(e.g., youth and young adults), socioeconomic status, race, ethnicity,
rurality, pregnancy status, current or prior military service, and
current or prior mental health conditions or substance use disorders.
* * * * *
0
3. Revise Sec. 1114.41 to read as follows:
Sec. 1114.41 Reporting requirements.
(a) * * *
(1) * * *
(vi) * * *
(C) Demographic characteristics of product(s) purchasers, such as
age, sex, race or ethnicity, geographic region, and tobacco use status;
* * * * *
(xvi) A summary of media tracking and optimization, by channel, by
product, and by audience demographics (e.g., age, sex, race/ethnicity,
geographic region), including a summary of any real-time digital media
monitoring and including a summary of implementation of any corrective
and preventive measures to identify, correct, and prevent delivery of
advertising to individuals below the minimum age of sale, not
previously submitted;
* * * * *
Robert F. Kennedy, Jr.,
Secretary, Department of Health and Human Services.
[FR Doc. 2026-08826 Filed 5-5-26; 8:45 am]
BILLING CODE 4164-01-P
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