84822 Federal Register / Vol. 89, No. 206 / Thursday, October 24, 2024 / Rules and Regulations 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

45 CFR Part 46 

RIN 0937–AA09 

Department of Health and Human 

Services Policy for the Protection of 

Human Research Subjects: Update to 

the Additional Protections for Specific 

Populations 

AGENCY: Department of Health and 

Human Services. 

ACTION: Final rule. 

SUMMARY: In this final rule, the 

Department of Health and Human 

Services (HHS) is amending its 

regulations that govern the protection of 

human subjects for conformity with 

2018 revisions made to the Federal 

policy for protection of human research 

subjects (the ‘‘Common Rule’’), as well 

as to maintain consistency with the 

prior version of the Common Rule for 

research that remains subject to those 

requirements. Amendments include 

updating citations that were 

renumbered, adding updated 

descriptions of the applicability of 

exemptions, and correcting a technical 

error. No substantive amendments are 

included in this final rule. 

DATES: This final rule is effective 

October 24, 2024. 

FOR FURTHER INFORMATION CONTACT: Julie 

Kaneshiro, Office for Human Research 

Protections (OHRP), Department of 

Health and Human Services, 1101 

Wootton Parkway, Suite 200, Rockville, 

MD 20852; telephone: 240–453–8293 or 

1–866–447–4777; facsimile: 240–453– 

8430; email Julie.kaneshiro@hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

A. Revision of the Common Rule 

The Common Rule, codified by HHS 

at subpart A of 45 CFR part 46, was 

revised by a final rule published in the 

Federal Register on January 19, 2017 

(82 FR 7149), and subsequently 

amended by an interim final rule 

published in the Federal Register on 

January 22, 2018 (83 FR 2885), and a 

final rule published on June 19, 2018 

(83 FR 28497). The revised Common 

Rule is defined in the regulatory text as 

the ‘‘2018 Requirements.’’ The prior 

version of the Common Rule, initially 

promulgated on June 18, 1991 (56 FR 

28002), and amended on June 23, 2005 

(70 FR 36325), published in the 2016 

Code of Federal Regulations and 

effective October 1, 2017, is defined by 

the revised Common Rule as the ‘‘pre2018 Requirements.’’ For brevity, in the 

regulatory text of subparts B, C, and D, 

HHS is shortening the full explanation 

of the ‘‘pre-2018 Requirements’’ to 

‘‘[t]he pre-2018 Requirements means 45 

CFR part 46, subpart A, as revised 

October 1, 2016’’ and the ‘‘2018 

Requirements’’ to ‘‘[t]he 2018 

Requirements means 45 CFR part 46, 

subpart A, as revised October 1, 2018.’’ 

The applicability of the pre-2018 or 

2018 Requirements is defined by 

§ 46.101(l) of the 2018 Requirements. 

Importantly, research that was approved 

under the pre-2018 Requirements may 

continue to follow that rule for the 

duration of the study; however, research 

initiated on or after January 21, 2019, 

must comply with the 2018 

Requirements. 

The preamble of the January 19, 2017 

final rule indicated that, to the extent 

appropriate, HHS intended to amend 

the other subparts of the HHS human 

subjects protection regulations to align 

with the revisions to the Common Rule 

codified at subpart A. Through this final 

rule, HHS is updating subparts B, C, and 

D to reference both the pre-2018 

Requirements and the 2018 

Requirements, as appropriate. HHS 

intends to separately amend subpart E 

to conform with both the pre-2018 and 

2018 Requirements. 

B. Subparts B, C, and D Background 

Subpart B of 45 CFR part 46, 

‘‘Additional Protections for Pregnant 

Women, Human Fetuses and Neonates 

Involved in Research,’’ was first 

promulgated on August 8, 1975. The 

most recent revision to subpart B was 

published in the Federal Register on 

November 13, 2001 (66 FR 56775). 

On November 16, 1978, the then 

Department of Health, Education, and 

Welfare published a final rule 

promulgating subpart C, ‘‘Additional 

Protections Pertaining to Biomedical 

and Behavioral Research Involving 

Prisoners as Subjects’’ (43 FR 53652). 

On January 26, 1981, the Common Rule 

was first published, which substantially 

updated subpart A of 45 CFR part 46 (46 

FR 8366). As part of this update, HHS 

also published an amendment to 

subpart C in which citations were 

corrected or updated and other 

technical amendments were made. 

On March 8, 1983, HHS published the 

final rule promulgating subpart D, 

‘‘Additional Protections for Children 

Involved as Subjects in Research’’ (43 

FR 9814). 

II. Amendments to Subparts B, C, and 

D of 45 CFR Part 46 

As described above, HHS is amending 

subparts B, C, and D for conformity with 

both the pre-2018 and 2018 

Requirements. Through this rule, HHS 

is: 

• Adding language to subparts B, C, 

and D to specify when references to 

subpart A provisions refer to the pre2018 Requirements or the 2018 

Requirements. 

• Adding language to clarify the 

meaning of ‘‘pre-2018 Requirements’’ 

and ‘‘2018 Requirements.’’ 

• Updating language in subparts B, C, 

and D that explains the applicability of 

the exemptions to research regulated 

under each subpart to reflect the 

additional exemptions allowed by 

§ 46.104(b) of the 2018 Requirements. 

• Correcting a technical error 

contained in subpart D. 

A. Amendments to Subpart B 

In this final rule, HHS makes eight 

amendments to subpart B, ‘‘Additional 

Protections for Pregnant Women, 

Human Fetuses and Neonates Involved 

in Research.’’ First, 45 CFR 46.201(b) is 

amended to state that for purposes of 

this subpart, the pre-2018 Requirements 

means subpart A as published in the 

2016 edition of the Code of Federal 

Regulations. The version of subpart A 

referenced in the definition of the term 

‘‘2018 Requirements’’ refers to 45 CFR 

part 46, subpart A, as revised October 1, 

2018. Section 46.201(b)(1) is added to 

provide that research subject to the pre2018 Requirements may apply the 

exemptions at § 46.101(b)(1) through (6) 

of the pre-2018 Requirements, while 

§ 46.201(b)(2) is added to provide that 

research subject to the 2018 

Requirements may apply the 

exemptions at § 46.104(d)(1) through (8) 

of the 2018 Requirements. 

Second, § 46.202 is amended to clarify 

that the definitions found in § 46.102 of 

the pre-2018 Requirements or the 2018 

Requirements, as applicable, shall be 

applicable to this subpart. 

Third, § 46.202(h) is amended to 

clarify that if a neonate is viable then it 

may be included in research only to the 

extent permitted and in accordance with 

the requirements of subpart A of the 

pre-2018 Requirements or the 2018 

Requirements, as applicable, and 

subpart D of part 46. 

Fourth, § 46.204(d) is amended to 

clarify that the pregnant woman’s 

consent must be obtained in accordance 

with the informed consent provisions of 

subpart A of the pre-2018 Requirements 

or the 2018 Requirements, as applicable. 

Fifth, § 46.204(e) is amended to state 

that the consent of the pregnant woman 

and the father must be obtained in 

accordance with the informed consent 

provisions of subpart A of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, except that the father’s 


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consent need not be obtained if he is 

unable to consent for the reasons stated 

therein. 

Sixth, § 46.205(b)(2) is amended to 

state that the consent of either parent of 

the neonate or, if neither parent is able 

to consent because of unavailability, 

incompetence, or temporary incapacity, 

the legally effective informed consent of 

either parent’s legally authorized 

representative is obtained in accord 

with the pre-2018 Requirements or the 

2018 Requirements, as applicable, 

except that the consent of the father or 

his legally authorized representative 

need not be obtained if the pregnancy 

resulted from rape or incest. 

Seventh, references in subpart B at 

§ 46.205(c)(5) to subpart A’s waiver and 

alteration of consent provisions are 

updated to reflect conformity with the 

pre-2018 Requirements as well as the 

2018 Requirements. In order for the 

citation to be consistent with the section 

numbering of both the pre-2018 and 

2018 Requirements, the prior pinpoint 

citation to § 46.116(c) and (d) has been 

modified to instead refer to § 46.116 of 

both the pre-2018 and 2018 

Requirements. 

Finally, the language of subpart B at 

§ 46.205(d) has been revised to replace 

the reference to subpart A with 

reference to the pre-2018 Requirements 

or the 2018 Requirements, as applicable. 

B. Amendments to Subpart C 

In this final rule, HHS makes six 

amendments to subpart C, ‘‘Additional 

Protections Pertaining to Biomedical 

and Behavioral Research Involving 

Prisoners as Subjects.’’ 

First, 45 CFR 46.301(c) is revised to 

provide that the requirements of this 

subpart are in addition to those imposed 

under the other subparts, including the 

2018 Requirements and the pre-2018 

Requirements, as applicable. This 

section is further revised to provide that 

the term ‘‘pre-2018 Requirements’’ 

means subpart A as published in the 

2016 edition of the Code of Federal 

Regulations. The term ‘‘2018 

Requirements’’ refers to 45 CFR part 46, 

subpart A, as revised October 1, 2018. 

Second, § 46.304 is modified to clarify 

that in addition to satisfying the 

requirements in § 46.107 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, an institutional review 

board (IRB), carrying out responsibilities 

with respect to this subpart, shall also 

meet the specific requirements further 

detailed in this section. 

Third, § 46.306(a) is modified to add 

the word ‘‘nonexempt’’ in order to 

clarify that, except for research 

involving prisoners that qualifies for 

exemption, research subject to subpart C 

must involve only a category of research 

reflected in 45 CFR 46.306(a)(2)(i) 

through (iv). 

Fourth, § 46.306(b) is revised to 

provide that research conducted or 

supported by DHHS (the Department of 

Health and Human Services) shall not 

involve prisoners except as provided in 

§ 46.306(b)(1) and (2). 

Fifth, § 46.306(b)(1) is added to state 

that for research subject to the pre-2018 

Requirements and this subpart, except 

as provided in § 46.306(a), biomedical 

or behavioral research conducted or 

supported by DHHS shall not involve 

prisoners as subjects. 

Sixth, § 46.306(b)(2) is added to state 

that for research subject to the 2018 

Requirements and this subpart, except 

as provided in § 46.306(a) or for 

research that is exempt pursuant to 

§ 46.104(b)(2) and (d)(1) through (8), 

biomedical or behavioral research 

conducted or supported by DHHS shall 

not involve prisoners as subjects. 

C. Amendments to Subpart D 

In this final rule, HHS makes 12 

amendments to subpart D, ‘‘Additional 

Protections for Children Involved as 

Subjects in Research.’’ 

First, HHS revises 45 CFR 46.401(a) to 

provide that the term ‘‘pre-2018 

Requirements’’ means subpart A as 

published in the 2016 edition of the 

Code of Federal Regulations; and that 

the term ‘‘2018 Requirements’’ means 45 

CFR part 46, subpart A, as revised 

October 1, 2018. 

Second, given that there is a new 

§ 46.401(a), the language of the previous 

§ 46.401(a)(1) and (2) is renumbered as 

§ 46.401(b)(1) and (2). 

Third, HHS is correcting a technical 

error in the renumbered § 46.401(b)(2) 

in the citation to the provision of 

subpart A that allows the Secretary to 

waive some or all regulatory 

requirements. Subpart D cites the 

provision as § 46.101(e). However, the 

Secretarial waiver provision in subpart 

A appears at § 46.101(i), not § 46.101(e), 

in both the pre-2018 and the 2018 

Requirements. This rule corrects this 

technical error, and revises the reference 

to ‘‘subpart A’’ to instead reference the 

pre-2018 and 2018 Requirements. 

Fourth, 45 CFR 46.401(c) is amended 

to include an explanation of how the 

exemptions provided in the pre-2018 

Requirements and the 2018 

Requirements apply to research 

regulated by subpart D. 

Fifth, § 46.401(c)(1) is added to 

provide that, for research subject to the 

pre-2018 Requirements, the exemptions 

at § 46.101(b)(1) and (3) through (6) of 

the pre-2018 Requirements are 

applicable to research subject to subpart 

D. In addition, the exemption at 

§ 46.101(b)(2) of the pre-2018 

Requirements regarding educational 

tests is also applicable to research 

subject to subpart D, with the caveat 

that the exemption at § 46.101(b)(2) for 

research involving survey or interview 

procedures or observations of public 

behavior does not apply to research 

subject to subpart D, except for research 

involving observation of public behavior 

when the investigator(s) does (do) not 

participate in the activities being 

observed. 

Sixth, § 46.401(c)(2) is added to 

provide that, for research subject to the 

2018 Requirements, the exemptions at 

§ 46.104(d)(1), (4), (5), (6), (7), and (8) of 

the 2018 Requirements may be applied 

to research subject to subpart D; the 

exemptions at § 46.104(d)(2)(i) and (ii) 

of the 2018 Requirements may only 

apply to research subject to this subpart 

involving educational tests or the 

observation of public behavior when the 

investigator(s) does (do) not participate 

in the activities being observed; and the 

exemptions at §§ 46.104(d)(2)(iii) and 

(d)(3) of the 2018 Requirements may not 

be applied to research subject to this 

subpart. 

Seventh, the language formerly found 

at 45 CFR 46.401(c) has been updated to 

reference the pre-2018 Requirements 

and the 2018 Requirements, instead of 

‘‘subpart A,’’ and moved to a new 

§ 46.401(d). 

Eighth, 45 CFR 46.402 is revised to 

provide that the definitions in § 46.102 

of the pre-2018 Requirements and 

§ 46.102 of the 2018 Requirements, as 

applicable, shall be applicable to this 

subpart. 

Ninth, 45 CFR 46.408(a) is modified 

to provide that even where the IRB 

determines that the subjects are capable 

of assenting, the IRB may still waive the 

assent requirement under circumstances 

in which consent may be waived in 

accord with § 46.116 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable. 

Tenth, § 46.408(b) is modified to 

provide that in addition to the 

determinations required under other 

applicable sections of this subpart, the 

IRB shall determine, in accordance with 

and to the extent that consent is 

required by § 46.116 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, that adequate provisions 

are made for soliciting the permission of 

each child’s parents or guardian. 

Eleventh, § 46.408(c) is modified to 

provide that in addition to the 

provisions for waiver contained in 

§ 46.116 of the pre-2018 Requirements 

or the 2018 Requirements, as applicable, 

if the IRB determines that a research 


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protocol is designed for conditions or 

for a subject population for which 

parental or guardian permission is not a 

reasonable requirement to protect the 

subjects (e.g., neglected or abused 

children), it may waive the consent 

requirements in § 46.116 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, and § 46.408(b), provided 

an appropriate mechanism for 

protecting the children who will 

participate as subjects in the research is 

substituted, and provided further that 

the waiver is not inconsistent with 

Federal, State, or local law. 

Twelfth, § 46.408(d) is modified to 

provide that permission by parents or 

guardians shall be documented in 

accordance with, and to the extent 

required by, § 46.117 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable. 

III. Legal Authority 

The legal authority is as follows: 5 

U.S.C. 301; 42 U.S.C. 289(a); 42 U.S.C. 

300v–1(b). 

IV. 5 U.S.C. 553(b)(B) of the 

Administrative Procedure Act, 5 U.S.C. 

551–559 

HHS finds that there is good cause to 

issue these amendments without 

advance notice and an opportunity for 

public comment. This final rule reflects 

changes that conform subparts B, C, and 

D to both the pre-2018 and 2018 

Requirements and correct a technical 

error in subpart D that predates the 

publication of the 2018 Requirements. 

This final rule merely (i) adds language 

to each subpart specifying how the 

regulatory exemptions and provisions 

apply under the pre-2018 or 2018 

Requirements, as applicable; (ii) corrects 

an erroneous citation in subpart D; and 

(iii) changes the citation to the subpart 

A provisions that allow waiver and 

alteration of informed consent in 

§ 46.205(c)(5) from § 46.116(c) and (d) to 

§ 46.116, in order to generally reference 

the waiver and alteration of informed 

consent provisions in both the pre-2018 

and 2018 versions of the Common Rule. 

HHS determines that advance notice 

and public comment are unnecessary. 

Pursuant to 5 U.S.C. 553(b)(B) of the 

Administrative Procedure Act, HHS 

finds good cause to dispense with 

advance notice and public comment as 

these procedures are unnecessary, 

because this rule only serves to update 

subparts B, C, and D to conform with 

provisions in the pre-2018 and 2018 

Requirements of 45 CFR part 46, which 

are already in effect, and to correct a 

citation error. HHS further finds good 

cause for this rule to be effective upon 

publication in accordance with 5 U.S.C. 

553(d)(3) because the provisions of the 

pre-2018 and 2018 Requirements to 

which these revisions conform are 

already in effect, and regulated entities 

already are required to comply with 

these provisions. 

V. Regulatory Impact Analyses 

We have examined the effects of this 

final rule under Executive Order 12866 

on Regulatory Planning and Review 

(September 30, 1993), Executive Order 

13563 on Improving Regulation and 

Regulatory Review (January 18, 2011), 

Executive Order 14094 on Modernizing 

Regulatory Review (April 6, 2023), the 

Paperwork Reduction Act of 1995 (Pub. 

L. 104–13), the Regulatory Flexibility 

Act, (Pub. L. 96–354, September 19, 

1980), the Congressional Review Act (5 

U.S.C. 801, Pub. L. 104–121), the 

Unfunded Mandates Reform Act of 1995 

(Pub. L. 104–4), Executive Order 13132 

on Federalism (August 4, 1999), and 

section 1102(b) of the Social Security 

Act. 

A. Executive Orders 12866, 13563, and 

14094 

Executive Orders 12866, 13563, and 

14094 direct agencies to assess all 

benefits, costs, and transfers of available 

regulatory alternatives and, when 

regulation is necessary, to select 

regulatory approaches that maximize 

net benefits (including potential 

economic, environmental, public health 

and safety, and other advantages; 

distributive impacts; and equity). Rules 

are ‘‘significant’’ under Executive Order 

12866 section 3(f)(1) (as amended by 

Executive Order 14094) if they have an 

annual effect on the economy of $200 

million or more (adjusted every 3 years 

by the Administrator of the Office of 

Information and Regulatory Affairs 

(OIRA) for changes in gross domestic 

product); 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, territorial, or tribal 

governments or communities. 

This rule makes technical corrections 

to subparts B, C, and D that reflect 

existing requirements contained in the 

2018 Requirements. The impacts of the 

2018 Requirements are accounted for in 

three prior regulatory impact analyses 

(82 FR 7231, 83 FR 2880, 83 FR 28505). 

Compared to a baseline scenario of the 

2018 Requirements, HHS finds that this 

rule will not have an impact on human 

subjects research or human subjects 

research review. This rule has not been 

designated as a ‘‘significant regulatory 

action’’ under section 3(f) of Executive 

Order 12866 (as amended by Executive 

Order 14094). 

B. Paperwork Reduction Act 

This final rule does not impose any 

additional information collection 

burden under the Paperwork Reduction 

Act and does not contain any 

information collection activities beyond 

the information collection already 

approved by Office of Management and 

Budget under control numbers 0990– 

0260, 0990–0473 and 0990–0481. 

C. Regulatory Flexibility Act 

The Regulatory Flexibility Act (5 

U.S.C. 601 et seq.) (RFA) and the Small 

Business Regulatory Enforcement 

Fairness Act of 1996, which amended 

the RFA, require agencies that issue a 

regulation to analyze options for 

regulatory relief for small businesses. If 

a rule has a significant impact on a 

substantial number of small entities, 

agencies must specifically consider the 

economic effect of the rule on small 

entities and analyze regulatory options 

that could lessen the impact of the rule. 

The RFA generally defines a ‘‘small 

entity’’ as (1) a proprietary firm meeting 

the size standards of the Small Business 

Administration; (2) a nonprofit 

organization that is not dominant in its 

field; or (3) a small government 

jurisdiction with a population of less 

than 50,000 (states and individuals are 

not included in the definition of ‘‘small 

entity’’). HHS considers a rule to have 

a significant economic impact on a 

substantial number of small entities if at 

least 5 percent of small entities 

experience an impact of more than 3 

percent of revenue. In making this 

determination, the impact of concern is 

any significant adverse economic 

impact on small entities. An agency may 

certify that a rule will not have a 

significant economic impact on a 

substantial number of small entities if 

the rule relieves regulatory burden, has 

no net burden, or otherwise has a 

positive economic effect on the small 

entities subject to the rule. 

This action does not have a significant 

economic impact on a substantial 

number of small entities under the RFA. 

Therefore, the regulatory flexibility 

analysis provided for under the RFA is 

not required. 

D. Unfunded Mandates Reform Act 

Section 202(a) of the Unfunded 

Mandates Reform Act (UMRA) of 1995 

requires that agencies 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 


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or more (adjusted annually for inflation) 

in any one year.’’ The current threshold 

after adjustment for inflation is $183 

million, using the 2023 implicit price 

deflator for the gross domestic product. 

We do not expect this final rule to result 

in expenditures that will exceed this 

amount. This action does not contain 

any unfunded mandate as described in 

UMRA, 2 U.S.C. 1531–1538, and does 

not significantly or uniquely affect small 

governments. 

E. Executive Order 13132: Federalism 

Executive Order 13132 establishes 

certain requirements that an agency 

must meet when it promulgates a rule 

that imposes substantial direct 

requirement costs on State and local 

governments or has federalism 

implications. HHS has determined that 

this rule does not contain policies that 

have substantial direct effects on the 

States, on the relationship between the 

Federal Government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government. Accordingly, we 

have concluded that this final rule does 

not contain policies that have 

federalism implications as defined in 

the order and, consequently, a 

federalism summary impact statement is 

not required. 

List of Subjects in 45 CFR Part 46 

Human research subjects, Reporting 

and recordkeeping requirements, 

Research. 

For the reasons set forth in the 

preamble, the Department of Health and 

Human Services amends 45 CFR part 46 

as follows: 

PART 46—PROTECTION OF HUMAN 

SUBJECTS 

■ 1. The authority citation for part 46 

continues to read as follows: 

Authority: 5 U.S.C. 301; 42 U.S.C. 289(a); 

42 U.S.C. 300v–1(b). 

Subpart B—Additional Protections for 

Pregnant Women, Human Fetuses and 

Neonates Involved in Research 

■ 2. Amend § 46.201 by revising 

paragraph (b) to read as follows: 

§ 46.201 To what do these regulations 

apply? 

* * * * * 

(b) The pre-2018 Requirements means 

45 CFR part 46, subpart A, as revised 

October 1, 2016. The 2018 Requirements 

means 45 CFR part 46, subpart A, as 

revised October 1, 2018. 

(1) For research subject to the pre2018 Requirements and this subpart, the 

exemptions at § 46.101(b)(1) through (6) 

of the pre-2018 Requirements are 

applicable to this subpart. 

(2) For research subject to the 2018 

Requirements and this subpart, the 

exemptions at § 46.104(d)(1) through (8) 

of the 2018 Requirements may be 

applied. 

* * * * * 

■ 3. Amend § 46.202 by revising the 

introductory text and paragraph (h) to 

read as follows: 

§ 46.202 Definitions. 

The definitions in § 46.102 of the pre2018 Requirements and the 2018 

Requirements, as applicable, shall be 

applicable to this subpart as well. In 

addition, as used in this subpart: 

* * * * * 

(h) Viable, as it pertains to the 

neonate, means being able, after 

delivery, to survive (given the benefit of 

available medical therapy) to the point 

of independently maintaining heartbeat 

and respiration. The Secretary may from 

time to time, taking into account 

medical advances, publish in the 

Federal Register guidelines to assist in 

determining whether a neonate is viable 

for purposes of this subpart. If a neonate 

is viable then it may be included in 

research only to the extent permitted 

and in accordance with the 

requirements of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, and subpart D of this part. 

■ 4. Amend § 46.204 by revising 

paragraphs (d) and (e) to read as follows: 

§ 46.204 Research involving pregnant 

women or fetuses. 

* * * * * 

(d) If the research holds out the 

prospect of direct benefit to the 

pregnant woman, the prospect of a 

direct benefit both to the pregnant 

woman and the fetus, or no prospect of 

benefit for the woman nor the fetus 

when risk to the fetus is not greater than 

minimal and the purpose of the research 

is the development of important 

biomedical knowledge that cannot be 

obtained by any other means, her 

consent is obtained in accord with the 

informed consent provisions of the pre2018 Requirements or the 2018 

Requirements, as applicable; 

(e) If the research holds out the 

prospect of direct benefit solely to the 

fetus then the consent of the pregnant 

woman and the father is obtained in 

accord with the informed consent 

provisions of the pre-2018 Requirements 

or the 2018 Requirements, as applicable, 

except that the father’s consent need not 

be obtained if he is unable to consent 

because of unavailability, 

incompetence, or temporary incapacity 

or the pregnancy resulted from rape or 

incest; 

* * * * * 

■ 5. Amend § 46.205 by revising 

paragraphs (b)(2), (c)(5), and (d) to read 

as follows: 

§ 46.205 Research involving neonates. 

* * * * * 

(b) * * * 

(2) The legally effective informed 

consent of either parent of the neonate 

or, if neither parent is able to consent 

because of unavailability, 

incompetence, or temporary incapacity, 

the legally effective informed consent of 

either parent’s legally authorized 

representative is obtained in accord 

with the pre-2018 Requirements or the 

2018 Requirements, as applicable, 

except that the consent of the father or 

his legally authorized representative 

need not be obtained if the pregnancy 

resulted from rape or incest. 

(c) * * * 

(5) The legally effective informed 

consent of both parents of the neonate 

is obtained in accord with the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, except that the waiver 

and alteration provisions of § 46.116 of 

the pre-2018 Requirements or the 2018 

Requirements do not apply. However, if 

either parent is unable to consent 

because of unavailability, 

incompetence, or temporary incapacity, 

the informed consent of one parent of a 

nonviable neonate will suffice to meet 

the requirements of this paragraph 

(c)(5), except that the consent of the 

father need not be obtained if the 

pregnancy resulted from rape or incest. 

The consent of a legally authorized 

representative of either or both of the 

parents of a nonviable neonate will not 

suffice to meet the requirements of this 

paragraph (c)(5). 

(d) Viable neonates. A neonate, after 

delivery, that has been determined to be 

viable may be included in the research 

only to the extent permitted by and in 

accord with the requirements of the pre2018 Requirements or the 2018 

Requirements, as applicable, and 

subpart D of this part. 

Subpart C—Additional Protections 

Pertaining to Biomedical and 

Behavioral Research Involving 

Prisoners as Subjects 

■ 6. Amend § 46.301 by revising 

paragraph (c) to read as follows: 

§ 46.301 Applicability. 

* * * * * 

(c) The requirements of this subpart 

are in addition to those imposed under 

the other subparts in this part and 


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84826 Federal Register / Vol. 89, No. 206 / Thursday, October 24, 2024 / Rules and Regulations 

includes the pre-2018 Requirements and 

the 2018 Requirements, as applicable. 

The pre-2018 Requirements means 45 

CFR part 46, subpart A, as revised 

October 1, 2016. The 2018 Requirements 

means 45 CFR part 46, subpart A, as 

revised October 1, 2018. 

■ 7. Amend § 46.304 by revising the 

introductory text to read as follows: 

§ 46.304 Composition of Institutional 

Review Boards where prisoners are 

involved. 

In addition to satisfying the 

requirements in § 46.107 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable, an Institutional Review 

Board, carrying out responsibilities with 

respect to this subpart, shall also meet 

the following specific requirements: 

* * * * * 

■ 8. Amend § 46.306 by revising 

paragraphs (a) introductory text and (b) 

to read as follows: 

§ 46.306 Permitted research involving 

prisoners. 

(a) Nonexempt biomedical or 

behavioral research conducted or 

supported by DHHS may involve 

prisoners as subjects only if: 

* * * * * 

(b) Biomedical or behavioral research 

conducted or supported by DHHS shall 

not involve prisoners except as follows: 

(1) For research subject to the pre2018 Requirements and this subpart, 

except as provided in paragraph (a) of 

this section, biomedical or behavioral 

research conducted or supported by 

DHHS shall not involve prisoners as 

subjects. 

(2) For research subject to the 2018 

Requirements and this subpart, except 

as provided in paragraph (a) of this 

section or for research that is exempt 

pursuant to § 46.104(b)(2) and (d)(1) 

through (8) of the 2018 Requirements, 

biomedical or behavioral research 

conducted or supported by DHHS shall 

not involve prisoners as subjects. 

Subpart D—Additional Protections for 

Children Involved as Subjects in 

Research 

■ 9. Revise § 46.401 to read as follows: 

§ 46.401 To what does this subpart apply? 

(a) The pre-2018 Requirements means 

45 CFR part 46, subpart A, as revised 

October 1, 2016. The 2018 Requirements 

means 45 CFR part 46, subpart A, as 

revised October 1, 2018. 

(b) This subpart applies to all research 

involving children as subjects, 

conducted or supported by the 

Department of Health and Human 

Services. 

(1) This includes research conducted 

by Department employees, except that 

each head of an Operating Division of 

the Department may adopt such 

nonsubstantive, procedural 

modifications as may be appropriate 

from an administrative standpoint. 

(2) It also includes research 

conducted or supported by the 

Department of Health and Human 

Services outside the United States, but 

in appropriate circumstances, the 

Secretary may, under § 46.101(i) of the 

pre-2018 Requirements or the 2018 

Requirements, waive the applicability of 

some or all of the requirements of this 

subpart for research of this type. 

(c) The application of the exemptions 

to this subpart is as follows: 

(1) For research subject to the pre2018 Requirements and this subpart, the 

exemptions at § 46.101(b)(1) and (b)(3) 

through (6) of the pre-2018 

Requirements are applicable to this 

subpart. The exemption at § 46.101(b)(2) 

of the pre-2018 Requirements regarding 

educational tests also is applicable to 

this subpart. However, the exemption at 

§ 46.101(b)(2) for research involving 

survey or interview procedures or 

observations of public behavior does not 

apply to research covered by this 

subpart, except for research involving 

observation of public behavior when the 

investigator(s) do not participate in the 

activities being observed. 

(2) For research subject to the 2018 

Requirements and this subpart, the 

exemptions at § 46.104(d)(1), (4), (5), (6), 

(7), and (8) of the 2018 Requirements are 

applicable to this subpart. The 

exemptions at § 46.104(d)(2)(i) and (ii) 

of the 2018 Requirements may only 

apply to research subject to this subpart 

that involves educational tests or the 

observation of public behavior when the 

investigator(s) do not participate in the 

activities being observed. The 

exemptions at § 46.104(d)(2)(iii) and 

(d)(3) of the 2018 Requirements may not 

be applied to research subject to this 

subpart. 

(d) The exceptions, additions, and 

provisions for waiver as they appear in 

§ 46.101(c) through (i) of the pre-2018 

Requirements or the 2018 Requirements 

are applicable to this subpart. 

■ 10. Amend § 46.402 by revising the 

introductory text to read as follows: 

§ 46.402 Definitions. 

The definitions in § 46.102 of the pre2018 Requirements and the 2018 

Requirements, as applicable, shall be 

applicable to this subpart as well. In 

addition, as used in this subpart: 

* * * * * 

■ 11. Amend § 46.408 by revising 

paragraphs (a) through (d) to read as 

follows: 

§ 46.408 Requirements for permission by 

parents or guardians and for assent by 

children. 

(a) In addition to the determinations 

required under other applicable sections 

of this subpart, the IRB shall determine 

that adequate provisions are made for 

soliciting the assent of the children, 

when in the judgment of the IRB the 

children are capable of providing assent. 

In determining whether children are 

capable of assenting, the IRB shall take 

into account the ages, maturity, and 

psychological state of the children 

involved. This judgment may be made 

for all children to be involved in 

research under a particular protocol, or 

for each child, as the IRB deems 

appropriate. If the IRB determines that 

the capability of some or all of the 

children is so limited that they cannot 

reasonably be consulted or that the 

intervention or procedure involved in 

the research holds out a prospect of 

direct benefit that is important to the 

health or well-being of the children and 

is available only in the context of the 

research, the assent of the children is 

not a necessary condition for proceeding 

with the research. Even where the IRB 

determines that the subjects are capable 

of assenting, the IRB may still waive the 

assent requirement under circumstances 

in which consent may be waived in 

accord with § 46.116 of the pre-2018 

Requirements or of the 2018 

Requirements, as applicable. 

(b) In addition to the determinations 

required under other applicable sections 

of this subpart, the IRB shall determine, 

in accordance with and to the extent 

that consent is required by § 46.116 of 

the pre-2018 Requirements or the 2018 

Requirements, as applicable, that 

adequate provisions are made for 

soliciting the permission of each child’s 

parents or guardian. Where parental 

permission is to be obtained, the IRB 

may find that the permission of one 

parent is sufficient for research to be 

conducted under § 46.404 or § 46.405. 

Where research is covered by §§ 46.406 

and 46.407 and permission is to be 

obtained from parents, both parents 

must give their permission unless one 

parent is deceased, unknown, 

incompetent, or not reasonably 

available, or when only one parent has 

legal responsibility for the care and 

custody of the child. 

(c) In addition to the provisions for 

waiver contained in § 46.116 of the pre2018 Requirements or the 2018 

Requirements, as applicable, if the IRB 

determines that a research protocol is 


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Federal Register / Vol. 89, No. 206 / Thursday, October 24, 2024 / Rules and Regulations 84827 

designed for conditions or for a subject 

population for which parental or 

guardian permission is not a reasonable 

requirement to protect the subjects (for 

example, neglected or abused children), 

it may waive the consent requirements 

in § 46.116 of the pre-2018 

Requirements or 2018 Requirements, as 

applicable, and paragraph (b) of this 

section, provided an appropriate 

mechanism for protecting the children 

who will participate as subjects in the 

research is substituted, and provided 

further that the waiver is not 

inconsistent with Federal, State, or local 

law. The choice of an appropriate 

mechanism would depend upon the 

nature and purpose of the activities 

described in the protocol, the risk and 

anticipated benefit to the research 

subjects, and their age, maturity, status, 

and condition. 

(d) Permission by parents or 

guardians shall be documented in 

accordance with and to the extent 

required by § 46.117 of the pre-2018 

Requirements or the 2018 Requirements, 

as applicable. 

* * * * * 

Xavier Beccera, 

Secretary, U.S. Department of Health and 

Human Services. 

[FR Doc. 2024–24399 Filed 10–23–24; 8:45 am] 

BILLING CODE 4150–36–P 


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