Code of Federal Regulations

TITLE 45

PUBLIC WELFARE

Department of Health and Human Services

PART 46

PROTECTION OF HUMAN SUBJECTS

* * *

Revised January 15, 2009

Effective July 14, 2009

SUBPART A—

Basic HHS Policy for Protec-

tion of Human Research

Subjects

Sec.

46.101 To what does this policy apply?

46.102 Definitions.

46.103 Assuring compliance with this

policy—research conducted or

supported by any Federal Depart-

ment or Agency.

46.104- [Reserved]

46.106

46.107 IRB membership.

46.108 IRB functions and operations.

46.109 IRB review of research.

46.110 Expedited review procedures for

certain kinds of research involving

no more than minimal risk, and for

minor changes in approved re-

search.

46.111 Criteria for IRB approval of

research.

46.112 Review by institution.

46.113 Suspension or termination of

IRB approval of research.

46.114 Cooperative research.

46.115 IRB records.

46.116 General requirements for in-

formed consent.

46.117 Documentation of informed

consent.

46.118 Applications and proposals lack-

ing definite plans for involvement

of human subjects.

46.119 Research undertaken without

the intention of involving human

subjects.

46.120 Evaluation and disposition of

applications and proposals for re-

search to be conducted or sup-

ported by a Federal Department or

Agency.

46.121 [Reserved]

46.122 Use of Federal funds.

46.123 Early termination of research

support: Evaluation of applica-

tions and proposals.

46.124 Conditions.

SUBPART B—

Additional Protections for

Pregnant Women, Human Fe-

tuses and Neonates Involved

in Research

Sec.

46.201 To what do these regulations

apply?

46.202 Definitions.

46.203 Duties of IRBs in connection

with research involving pregnant

women, fetuses, and neonates.

46.204 Research involving pregnant

women or fetuses.

46.205 Research involving neonates.

46.206 Research involving, after deliv-

ery, the placenta, the dead fetus or

fetal material.

46.207 Research not otherwise approv-

able which presents an opportunity

to understand, prevent, or alleviate

a serious problem affecting the

health or welfare of pregnant

women, fetuses, or neonates.

SUBPART C—

Additional Protections

Pertaining to Biomedical and

Behavioral Research Involv-

ing

Prisoners as Subjects

Sec.

46.301 Applicability.

46.302 Purpose.

46.303 Definitions.

46.304 Composition of Institutional

Review Boards where prisoners

are involved.

46.305 Additional duties of the Insti-

tutional Review Boards where

prisoners are involved.

46.306 Permitted research involving

prisoners.

SUBPART D—

Additional Protections

for Children Involved as Sub-

jects

in Research

Sec.

46.401 To what do these regulations

apply?

46.402 Definitions.

46.403 IRB duties.

46.404 Research not involving greater

than minimal risk.

46.405 Research involving greater

than minimal risk but presenting

the prospect of direct benefit to

the individual subjects.

46.406 Research involving greater

than minimal risk and no pros-

pect of direct benefit to individ-

ual subjects, but likely to yield

generalizable knowledge about

the subject’s disorder or condi-

tion.

46.407 Research not otherwise ap-

provable which presents an op-

portunity to understand, prevent,

or alleviate a serious problem

affecting the health or welfare of

children.

46.408 Requirements for permission

by parents or guardians and for

assent by children.

46.409 Wards.

Authority: 5 U.S.C. 301; 42 U.S.C. 289

(a).

SUBPART E —

Registration of Institutional

Review Boards

Sec.

46.501 What IRBs must be registered?

46.502 What information must be

provided when registering an

IRB?

46.503 When must an IRB be regis-

tered?

46.504 How must an IRB be regis-

tered?

46.505 When must IRB registration

information be renewed or up-

dated?

Editorial Note: The Department of

Health and Human Services issued a

notice of waiver regarding the require-

ments set forth in part 46, relating to

protection of human subjects, as they

pertain to demonstration projects,

approved under section 1115 of the

Social Security Act, which test the use

of cost-sharing, such as deductibles,

copayment and coinsurance, in the

Medicaid program. For further infor-

mation see 47 FR 9208, Mar. 4, 1982.

2 45 CFR 46

SUBPART A

Basic HHS Policy for Protection

of Human Research Subjects

Authority: 5 U.S.C. 301; 42 U.S.C. 289;

42 U.S.C. 300v-1(b).

Source: 56 FR 28012, 28022, June 18, 1991,

unless otherwise noted.

§46.101 To what does this policy apply?

(a) Except as provided in paragraph (b) of

this section, this policy applies to all research

involving human subjects conducted, sup-

ported or otherwise subject to regulation by

any federal department or agency which

takes appropriate administrative action to

make the policy applicable to such research.

This includes research conducted by federal

civilian employees or military personnel,

except that each department or agency head

may adopt such procedural modifications as

may be appropriate from an administrative

standpoint. It also includes research con-

ducted, supported, or otherwise subject to

regulation by the federal government outside

the United States.

(1) Research that is conducted or sup-

ported by a federal department or agency,

whether or not it is regulated as defined in

§46.102(e), must comply with all sections

of this policy.

(2) Research that is neither conducted nor

supported by a federal department or

agency but is subject to regulation as de-

fined in §46.102(e) must be reviewed and

approved, in compliance with §46.101,

§46.102, and §46.107 through §46.117 of

this policy, by an institutional review

board (IRB) that operates in accordance

with the pertinent requirements of this

policy.

(b) Unless otherwise required by department

or agency heads, research activities in which

the only involvement of human subjects will

be in one or more of the following catego-

ries are exempt from this policy:

(1) Research conducted in established or

commonly accepted educational settings,

involving normal educational practices,

such as (i) research on regular and special

education instructional strategies, or (ii)

research on the effectiveness of or the

comparison among instructional tech-

niques, curricula, or classroom manage-

ment methods.

(2) Research involving the use of educa-

tional tests (cognitive, diagnostic, aptitude,

achievement), survey procedures, inter-

view procedures or observation of public

behavior, unless: (i) information obtained

is recorded in such manner that human

subjects can be identified, directly or

through identifiers linked to the subjects;

and (ii) any disclosure of the human sub-

jects’ responses outside the research could

reasonably place the subjects at risk of

criminal or civil liability or be damaging to

the subjects’ financial standing, employ-

ability, or reputation.

(3) Research involving the use of educa-

tional tests (cognitive, diagnostic, aptitude,

achievement), survey procedures, inter-

view procedures, or observation of public

behavior that is not exempt under para-

graph (b)(2) of this section, if:

(i) the human subjects are elected or ap-

pointed public officials or candidates for

public office; or (ii) federal statute(s) re-

quire(s) without exception that the confi-

dentiality of the personally identifiable

information will be maintained through-

out the research and thereafter.

(4) Research involving the collection or

study of existing data, documents, records,

pathological specimens, or diagnostic

specimens, if these sources are publicly

available or if the information is recorded

by the investigator in such a manner that

subjects cannot be identified, directly or

through identifiers linked to the subjects.

(5) Research and demonstration projects

which are conducted by or

subj

ect to the

approval of department or agency heads,

and which are designed to study, evaluate,

or otherwise examine:(i) Public benefit or

service programs; (ii) procedures for ob-

taining benefits or services under those

programs; (iii) possible changes in or alter-

natives to those programs or procedures;

or (iv) possible changes in methods or

levels of payment for benefits or services

under those programs.

(6) Taste and food quality evaluation and

consumer acceptance studies, (i) if whole-

some foods without additives are con-

sumed or (ii) if a food is consumed that

contains a food ingredient at or below the

level and for a use found to be safe, or

agricultural chemical or environmental

contaminant at or below the level found

to be safe, by the Food and Drug Admini-

stration or approved by the Environ-

mental Protection Agency or the Food

Safety and Inspection Service of the U.S.

Department of Agriculture.

judgment as to whether a particular activity

is covered by this policy.

(d) Department or agency heads may require

that specific research activities or classes of

research activities conducted, supported, or

otherwise subject to regulation by the de-

partment or agency but not otherwise cov-

ered by this policy, comply with some or all

of the requirements of this policy.

(e) Compliance with this policy requires

compliance with pertinent federal laws or

regulations which provide additional protec-

tions for human subjects.

(f) This policy does not affect any state or

local laws or regulations which may other-

wise be applicable and which provide addi-

tional protections for human subjects.

(g) This policy does not affect any foreign

laws or regulations which may otherwise be

applicable and which provide additional

protections to human subjects of research.

h) When research covered by this policy

takes place in foreign countries, procedures

normally followed in the foreign countries

to protect human subjects may differ from

those set forth in this policy. [An example is

a foreign institution which complies with

guidelines consistent with the World Medi-

cal Assembly Declaration (Declaration of

Helsinki amended 1989) issued either by

sovereign states or by an organization whose

function for the protection of human re-

search subjects is internationally recognized.]

In these circumstances, if a department or

agency head determines that the procedures

prescribed by the institution afford protec-

tions that are at least equivalent to those

provided in this policy, the department or

agency head may approve the substitution of

the foreign procedures in lieu of the proce-

dural requirements provided in this policy.

Except when otherwise required by statute,

Executive Order, or the department or

agency head, notices of these actions as they

occur will be published in the FEDERAL

as provided in department or agency proce-

dures.

45 CFR 46 3

(i) Unless otherwise required by law, depart-

ment or agency heads may waive the appli-

cability of some or all of the provisions of

this policy to specific research activities or

classes of research activities otherwise cov-

ered by this policy. Except when otherwise

required by statute or Executive Order, the

department or agency head shall forward

advance notices of these actions to the Of-

fice for Human Research Protections, De-

partment of Health and Human Services

(HHS), or any successor office, and shall

also publish them in the FEDERAL REG-

ISTER or in such other manner as provided

in department or agency procedures.

[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June

28, 1991, as amended at 70 FR 36328, June 23, 2005]

§46.102 Definitions.

(a) Department or agency head means the head

of any federal department or agency and any

other officer or employee of any department

or agency to whom authority has been dele-

gated.

(b) Institution means any public or private

entity or agency (including federal, state, and

other agencies).

individual or judicial or other body author-

ized under applicable law to consent on

behalf of a prospective subject to the sub-

ject’s participation in the procedure(s) in-

volved in the research.

(d) Research means a systematic investigation,

including research development, testing and

evaluation, designed to develop or contrib-

ute to generalizable knowledge. Activities

which meet this definition constitute re-

search for purposes of this policy, whether

or not they are conducted or supported un-

der a program which is considered research

for other purposes. For example, some dem-

onstration and service programs may include

research activities.

(e) Research subject to regulation, and similar

terms are intended to encompass those re-

search activities for which a federal depart-

ment or agency has specific responsibility

for regulating as a research activity (for ex-

ample, Investigational New Drug require-

ments administered by the Food and Drug

Administration). It does not include research

activities which are incidentally regulated by

a federal department or agency solely as part

of the department’s or agency’s broader

responsibility to regulate certain types of

activities whether research or non-research

in nature (for example, Wage and Hour re-

quirements administered by the Department

of Labor).

(f) Human subject means a living individual

about whom an investigator (whether pro-

fessional or student) conducting research

obtains

(1) Data through intervention or interac-

tion with the individual, or

(2) Identifiable private information.

Intervention includes both physical procedures

by which data are gathered (for example,

venipuncture) and manipulations of the sub-

ject or the subject’s environment that are

performed for research purposes. Interac-

tion includes communication or interper-

sonal contact between investigator and sub-

ject. Private information includes informa-

tion about behavior that occurs in a context

in which an individual can reasonably expect

that no observation or recording is taking

place, and information which has been pro-

vided for specific purposes by an individual

and which the individual can reasonably

expect will not be made public (for example,

a medical record).

Private information must be individually identi-

fiable (i.e., the identity of the subject is or

may readily be ascertained by the investiga-

tor or associated with the information) in

order

for obtai

ning the information to con-

stitute research involving human subjects.

(g) IRB means an institutional review board

established in accord with and for the pur-

poses expressed in this policy.

(h) IRB approval means the determination of

the IRB that the research has been reviewed

and may be conducted at an institution

within the constraints set forth by the IRB

and by other institutional and federal re-

quirements.

(i) Minimal risk means that the probability

and magnitude of harm or discomfort antici-

pated in the research are not greater in and

of themselves than those ordinarily encoun-

tered in daily life or during the performance

of routine physical or psychological exami-

nations or tests.

h) When research covered by this policy

takes place in foreign countries, procedures

normally followed in the foreign countries

to protect human subjects may differ from

those set forth in this policy. [An example is

a foreign institution which complies with

guidelines consistent with the World Medi-

cal Assembly Declaration (Declaration of

Helsinki amended 1989) issued either by

sovereign states or by an organization whose

function for the protection of human re-

search subjects is internationally recognized.]

In these circumstances, if a department or

agency head determines that the procedures

prescribed by the institution afford protec-

tions that are at least equivalent to those

provided in this policy, the department or

agency head may approve the substitution of

the foreign procedures in lieu of the proce-

dural requirements provided in this policy.

Except when otherwise required by statute,

Executive Order, or the department or

agency head, notices of these actions as they

occur will be published in the FEDERAL

as provided in department or agency proce-

dures.

Institutions with HHS-approved assurances on file will abide by provisions of Title 45 CFR part 46 subparts A-D. Some of the other departments and agencies have incor-

porated all provisions of Title 45 CFR part 46 into their policies and procedures as well. However, the exemptions at 45 CFR 46.101(b) do not apply to research involving

prisoners, subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or observation of public behavior, does not apply to

research with children, subpart D, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.

4 45 CFR 46

§46.103 Assuring compliance with this

policy -- research conducted or sup-

ported by any Federal Department

or Agency.

(a) Each institution engaged in research

which is covered by this policy and which is

conducted or supported by a federal depart-

ment or agency shall provide written assur-

ance satisfactory to the department or

agency head that it will comply with the

requirements set forth in this policy. In lieu

of requiring submission of an assurance,

individual department or agency heads shall

accept the existence of a current assurance,

appropriate for the research in question, on

file with the Office for Human Research

Protections, HHS, or any successor office,

and approved for federalwide use by that

office. When the existence of an HHS-

approved assurance is accepted in lieu of

requiring submission of an assurance, re-

ports (except certification) required by this

policy to be made to department and agency

heads shall also be made to the Office for

Human Research Protections, HHS, or any

successor office.

(b) Departments and agencies will conduct

or support research covered by this policy

only if the institution has an assurance ap-

proved as provided in this section, and only

if the institution has certified to the depart-

ment or agency head that the research has

been reviewed and approved by an IRB pro-

vided for in the assurance, and will be sub-

ject to continuing review by the IRB. Assur-

ances applicable to federally supported or

conducted research shall at a minimum in-

clude:

(1)A statement of principles governing the

institution in the discharge of its responsi-

bilities for protecting the rights and wel-

fare of human subjects of research con-

ducted at or sponsored by the institution,

regardless of whether the research is sub-

ject to Federal regulation. This may in-

clude an appropriate existing code, decla-

ration, or statement of ethical principles,

or a statement formulated by the institu-

tion itself. This requirement does not pre-

empt provisions of this policy applicable

to department- or agency-supported or

regulated research and need not be appli-

cable to any research exempted or waived

under §46.101(b) or (i).

(2)Designation of one or more IRBs estab-

lished in accordance with the requirements

of this policy, and for which provisions are

made for meeting space and sufficient

staff to support the IRB's review and re-

cordkeeping duties.

(3)A list of IRB members identified by

name; earned degrees; representative ca-

pacity; indications of experience such as

board certifications, licenses, etc., suffi-

cient to describe each member's chief an-

ticipated contributions to IRB delibera-

tions; and any employment or other rela-

tionship between each member and the

institution; for example: full-time em-

ployee, part-time employee, member of

governing panel or board, stockholder,

paid or unpaid consultant. Changes in IRB

membership shall be reported to the de-

partment or agency head, unless in accord

with §46.103(a) of this policy, the exis-

tence of an HHS-approved assurance is

accepted. In this case, change in IRB

membership shall be reported to the Of-

fice for Human Research Protections,

HHS, or any successor office.

(4)Written procedures which the IRB will

follow (i) for conducting its initial and

continuing review of research and for re-

porting its findings and actions to the in-

vestigator and the institution; (ii) for deter-

mining which projects require review more

often than ann

ually and

which projects

need verification from sources other than

the investigators that no material changes

have occurred since previous IRB review;

and (iii) for ensuring prompt reporting to

the IRB of proposed changes in a research

activity, and for ensuring that such

changes in approved research, during the

period for which IRB approval has already

been given, may not be initiated without

IRB review and approval except when

necessary to eliminate apparent immediate

hazards to the subject.

(5)Written procedures for ensuring

prompt reporting to the IRB, appropriate

institutional officials, and the department

or agency head of (i) any unanticipated

problems involving risks to subjects or

others or any serious or continuing non-

compliance with this policy or the require-

ments or determinations of the IRB; and

(ii) any suspension or termination of IRB

approval.

individual authorized to act for the institu-

tion and to assume on behalf of the institu-

tion the obligations imposed by this policy

and shall be filed in such form and manner

as the department or agency head prescribes.

(d) The department or agency head will

evaluate all assurances submitted in accor-

dance with this policy through such officers

and employees of the department or agency

and such experts or consultants engaged for

this purpose as the department or agency

head determines to be appropriate. The de-

partment or agency head's evaluation will

take into consideration the adequacy of the

proposed IRB in light of the anticipated

scope of the institution's research activities

and the types of subject populations likely to

be involved, the appropriateness of the pro-

posed initial and continuing review proce-

dures in light of the probable risks, and the

size and complexity of the institution.

(e) On the basis of this evaluation, the de-

partment or agency head may approve or

disapprove the assurance, or enter into ne-

gotiations to develop an approvable one.

The department or agency head may limit

the period during which any particular ap-

proved assurance or class of approved assur-

ances shall remain effective or otherwise

condition or restrict approval.

(f) Certification is required when the re-

search is supported by a federal department

or agency and not otherwise exempted or

waived under §46.101(b) or (i). An institu-

tion with an approved assurance shall certify

that each application or proposal for re-

search covered by the assurance and by

§46.103 of this Policy has been reviewed and

approved by the IRB. Such certification

must be submitted with the application or

proposal or by such later date as may be

prescribed by the department or agency to

which the application or proposal is submit-

ted. Under no condition shall research cov-

ered by §46.103 of the Policy be supported

prior to receipt of the certification that the

research has been reviewed and approved by

the IRB. Institutions without an approved

assurance covering the research shall certify

within 30 days after receipt of a request for

such a certification from the department or

agency, that the application or proposal has

been approved by the IRB. If the certifica-

tion is not submitted within these time lim-

its, the application or proposal may be re-

turned to the institution.

(Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June

28, 1991, as amended at 70 FR 36328, June 23, 2005]

§§46.104--46.106 [Reserved]

45 CFR 46 5

§46.107 IRB membership.

(a) Each IRB shall have at least five mem-

bers, with varying backgrounds to promote

complete and adequate review of research

activities commonly conducted by the insti-

tution. The IRB shall be sufficiently quali-

fied through the experience and expertise of

its members, and the diversity of the mem-

bers, including consideration of race, gender,

and cultural backgrounds and sensitivity to

such issues as community attitudes, to pro-

mote respect for its advice and counsel in

safeguarding the rights and welfare of hu-

man subjects. In addition to possessing the

professional competence necessary to review

specific research activities, the IRB shall be

able to ascertain the acceptability of pro-

posed research in terms of institutional com-

mitments 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 knowl-

edgeable about and experienced in working

with these 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 per-

sons of both sexes, so long as no selection is

made to the IRB on the basis of gender. No

IRB may consist entirely of members of one

profession.

ber whose primary concerns are in scientific

areas and at least one member whose pri-

mary concerns are in nonscientific areas.

(d) Each IRB shall include at least one mem-

ber who is not otherwise affiliated with the

institution and who is not part of the imme-

diate family of a person who is affiliated

with the institution.

(e) No IRB may have a member participate

in the IRB's initial or continuing review of

any project in which the member has a con-

flicting interest, except to provide informa-

tion requested by the IRB.

(f) An IRB may, in its discretion, invite indi-

viduals with competence in special areas to

assist in the review of issues which require

expertise beyond or in addition to that avail-

able on the IRB. These individuals may not

vote with the IRB

§46.108 IRB functions and operations.

In order to fulfill the requirements of this

policy each IRB shall:

(a) Follow written procedures in the same

detail as described in §46.103(b)(4) and, to

the extent required by, §46.103(b)(5).

(b) Except when an expedited review proce-

dure is used (see §46.110), review proposed

research at convened meetings at which a

majority of the members of the IRB are

present, including at least one member

whose primary concerns are in nonscientific

areas. In order for the research to be ap-

proved, it shall receive the approval of a

majority of those members present at the

meeting.

§46.109 IRB review of research.

(a) An IRB shall review and have authority

to approve, require modifications in (to se-

cure approval), or disapprove all research

activities covered by this policy.

(b) An IRB shall require that information

given to subjects as part of informed con-

sent is in accordance with §46.116. The IRB

may require that information, in addition to

that specifically mentioned in §46.116, be

given to the subjects when in the IRB's judg-

ment the information would meaningfully

add to the protection of the rights and wel-

fare of subjects.

informed consent

or may waiv

e documenta-

tion in accordance with §46.117.

(d) An IRB shall notify investigators and the

institution in writing of its decision to ap-

prove or disapprove the proposed research

activity, or of modifications required to se-

cure IRB approval of the research activity. If

the IRB decides to disapprove a research

activity, it shall include in its written notifica-

tion a statement of the reasons for its deci-

sion and give the investigator an opportunity

to respond in person or in writing.

(e) An IRB shall conduct continuing review

of research covered by this policy at inter-

vals appropriate to the degree of risk, but

not less than once per year, and shall have

authority to observe or have a third party

observe the consent process and the re-

search.

(Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005]

§46.110 Expedited review procedures for

certain kinds of research involving no

more than minimal risk, and for minor

changes in approved research.

(a) The Secretary, HHS, has established, and

published as a Notice in the FEDERAL

that may be reviewed by the IRB through an

expedited review procedure. The list will be

amended, as appropriate, after consultation

with other departments and agencies,

through periodic republication by the Secre-

tary, HHS, in the FEDERAL REGISTER.

A copy of the list is available from the Of-

fice for Human Research Protections, HHS,

or any successor office.

(b) An IRB may use the expedited review

procedure to review either or both of the

following:

(1) some or all of the research appearing

on the list and found by the reviewer(s) to

involve no more than minimal risk,

(2) minor changes in previously approved

research during the period (of one year or

less) for which approval is authorized.

Under an expedited review procedure, the

review may be carried out by the IRB chair-

person or by one or more experienced re-

viewers designated by the chairperson from

among members of the IRB. In reviewing

the research, the reviewers may exercise all

of the authorities of the IRB except that the

reviewers may not disapprove the research.

A research activity may be disapproved only

after review in accordance with the non-

expedited procedure set forth in §46.108(b).

view procedure shall adopt a method for

keeping all members advised of research

proposals which have been approved under

the procedure.

(d) The department or agency head may

restrict, suspend, terminate, or choose not to

authorize an institution's or IRB's use of the

expedited review procedure.

[

56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005]

§46.111 Criteria for IRB approval of re-

search.

(a) In order to approve research covered by

this policy the IRB shall determine that all of

the following requirements are satisfied:

(1) Risks to subjects are minimized: (i) By

using procedures which are consistent

with sound research design and which do

not unnecessarily expose subjects to risk,

and (ii) whenever appropriate, by using

procedures already being performed on

the subjects for diagnostic or treatment

purposes.

6 45 CFR 46

(2) Risks to subjects are reasonable in rela-

tion to anticipated benefits, if any, to sub-

jects, and the importance of the knowl-

edge that may reasonably be expected to

result. In evaluating risks and benefits, the

IRB should consider only those risks and

benefits that may result from the research

(as distinguished from risks and benefits of

therapies subjects would receive even if

not participating in the research). The IRB

should not consider possible long-range

effects of applying knowledge gained in

the research (for example, the possible

effects of the research on public policy) as

among those research risks that fall within

the purview of its responsibility.

(3) Selection of subjects is equitable. In

making this assessment the IRB should

take into account the purposes of the re-

search and the setting in which the re-

search will be conducted and should be

particularly cognizant of the special prob-

lems of research involving vulnerable

populations, such as children, prisoners,

pregnant women, mentally disabled per-

sons, or economically or educationally

disadvantaged persons.

(4) Informed consent will be sought from

each prospective subject or the subject's

legally authorized representative, in accor-

dance with, and to the extent required by

§46.116.

(5) Informed consent will be appropriately

documented, in accordance with, and to

the extent required by §46.117.

(6) When appropriate, the research plan

makes adequate provision for monitoring

the data collected to ensure the safety of

subjects.

(7) When appropriate, there are adequate

provisions to protect the privacy of sub-

jects and to maintain the confidentiality of

data.

(b) When some or all of the subjects are

likely to be vulnerable to coercion or undue

influence, such as children, prisoners, preg-

nant women, mentally disabled persons, or

economically or educationally disadvantaged

persons, additional safeguards have been

included in the study to protect the rights

and welfare of these subjects

§46.112 Review by institution.

Research covered by this policy that has

been approved by an IRB may be subject to

further appropriate review and approval or

disapproval by officials of the institution.

However, those officials may not approve

the research if it has not been approved by

an IRB.

§46.113 Suspension or termination of

IRB approval of research.

An IRB shall have authority to suspend or

terminate approval of research that is not

being conducted in accordance with the

IRB's requirements or that has been associ-

ated with unexpected serious harm to sub-

jects. Any suspension or termination of ap-

proval shall include a statement of the rea-

sons for the IRB's action and shall be re-

ported promptly to the investigator, appro-

priate institutional officials, and the depart-

ment or agency head.

(Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005]

§46.114 Cooperative research.

Cooperative research projects are those pro-

jects covered by this policy which involve

more than one institution. In the conduct of

cooperative research projects, each institu-

tion is responsible for safeguarding the

rights and welfare of human subjects and for

complying with this policy. With the ap-

proval of the department or agency head, an

institution participating in a cooperative

project may enter into a joint review ar-

rangement, rely upon the review of another

qualified IRB, or make similar arrangements

for avoiding duplication of effort.

§46.115 IRB records.

(a) An institution, or when appropriate an

IRB, shall prepare and maintain adequate

documentation of IRB activities, including

the following:

(1) Copies of all research proposals re-

viewed, scientific evaluations, if any, that

accompany the proposals, approved sam-

ple consent documents, progress reports

submitted by investigators, and reports of

injuries to subjects.

(2) Minutes of IRB meetings which shall

be in sufficient detail to show attendance

at the meetings; actions taken by the IRB;

the vote on these actions including the

number of members voting for, against,

and abstaining; the basis for requiring

changes in or disapproving research; and a

written summary of the discussion of con-

troverted issues and their resolution.

(3) Records of continuing review activities.

(4) Copies of all correspondence between

the IRB and the investigators.

(5) A list of IRB members in the same

detail as described in §46.103(b)(3).

(6) Written procedures for the IRB in the

same detail as described in §46.103(b)(4)

and §46.103(b)(5).

(7) Statements of significant new findings

provided to subjects, as required by

§46.116(b)(5).

(b) The records required by this policy shall

be retained for at least 3 years, and records

relating to research which is conducted shall

be retained for at least 3 years after comple-

tion of the research. All records shall be

accessible for inspection and copying by

authorized representatives of the depart-

ment or agency at reasonable times and in a

reasonable manner.

(

Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[

56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005]

§46.116 General requirements for in-

formed consent.

Except as provided elsewhere in this policy,

no investigator may involve a human being

as a subject in research covered by this pol-

icy unless the investigator has obtained the

legally effective informed consent of the

subject or the subject's legally authorized

representative. An investigator shall seek

such consent only under circumstances that

provide the prospective subject or the repre-

sentative sufficient opportunity to consider

whether or not to participate and that mini-

mize the possibility of coercion or undue

influence. The information that is given to

the subject or the representative shall be in

language understandable to the subject or

the representative. No informed consent,

whether oral or written, may include any

exculpatory language through which the

subject or the representative is made to

waive or appear to waive any of the subject's

legal rights, or releases or appears to release

the investigator, the sponsor, the institution

or its agents from liability for negligence.

(a) Basic elements of informed consent.

Except as provided in paragraph (c) or (d) of

this section, in seeking informed consent the

following information shall be provided to

each subject:

(1) A statement that the study involves

research, an explanation of the purposes

of the research and the expected duration

of the subject's participation, a description

of the procedures to be followed, and

identification of any procedures which are

experimental;

(2) A description of any reasonably fore-

seeable risks or discomforts to the subject;

(3) A description of any benefits to the

subject or to others which may reasonably

be expected from the research;

(4) A disclosure of appropriate alternative

procedures or courses of treatment, if any,

that might be advantageous to the subject;

(5) A statement describing the extent, if

any, to which confidentiality of records

identifying the subject will be maintained;

45 CFR 46 7

(6) For research involving more than mini-

mal risk, an explanation as to whether any

compensation and an explanation as to

whether any medical treatments are avail-

able if injury occurs and, if so, what they

consist of, or where further information

may be obtained;

(7) An explanation of whom to contact for

answers to pertinent questions about the

research and research subjects' rights, and

whom to contact in the event of a re-

search-related injury to the subject; and

(8) A statement that participation is volun-

tary, refusal to participate will involve no

penalty or loss of benefits to which the

subject is otherwise entitled, and the sub-

ject may discontinue participation at any

time without penalty or loss of benefits to

which the subject is otherwise entitled.

(b) Additional elements of informed con-

sent. When appropriate, one or more of the

following elements of information shall also

be provided to each subject:

(1) A statement that the particular treat-

ment or procedure may involve risks to

the subject (or to the embryo or fetus, if

the subject is or may become pregnant)

which are currently unforeseeable;

(2) Anticipated circumstances under which

the subject's participation may be termi-

nated by the investigator without regard to

the subject's consent;

(3) Any additional costs to the subject that

may result from participation in the re-

search;

(4) The consequences of a subject's deci-

sion to withdraw from the research and

procedures for orderly termination of par-

ticipation by the subject;

(5) A statement that significant new find-

ings developed during the course of the

research which may relate to the subject's

willingness to continue participation will

be provided to the subject; and

(6) The approximate number of subjects

involved in the study.

dure which does not include, or which alters,

some or all of the elements of informed

consent set forth above, or waive the re-

quirement to obtain informed consent pro-

vided the IRB finds and documents that:

(1) The research or demonstration project

is to be conducted by or subject to the

approval of state or local government offi-

cials and is designed to study, evaluate, or

otherwise examine: (i) public benefit or

service programs; (ii) procedures for ob-

taining benefits or services under those

programs; (iii) possible changes in or alter-

natives to those programs or procedures;

or (iv) possible changes in methods or

levels of payment for benefits or services

under those programs; and

(2) The research could not practicably be

carried out without the waiver or altera-

tion.

(d) An IRB may approve a consent proce-

dure which does not include, or which alters,

some or all of the elements of informed

consent set forth in this section, or waive

the requirements to obtain informed con-

sent provided the IRB finds and documents

that:

1) The research involves no more than mini-

mal risk to the subjects;

(2) The waiver or alteration will not ad-

versely affect the rights and welfare of the

subjects;

(3) The research could not practicably be

carried out without the waiver or alteration;

and

(4) Whenever appropriate, the subjects will

be provided with additional pertinent infor-

mation after participation.

(e) The informed consent requirements in

this policy are not intended to preempt any

applicable federal, state, or local laws which

require additional information to be dis-

closed in order for informed consent to be

legally effective.

(f) Nothing in this policy is intended to limit

the authority of a physician to provide emer-

gency medical care, to the extent the physi-

cian is permitted to do so under applicable

federal, state, or local law.

(Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005

]

§46.117 Documentation of informed con-

sent.

(a) Except as provided in paragraph (c) of

this section, informed consent shall be docu-

mented by the use of a written consent form

approved by the IRB and signed by the sub-

ject or the subject's legally authorized repre-

sentative. A copy shall be given to the per-

son signing the form.

(b) Except as provided in paragraph (c) of

this section, the consent form may be either

of the following:

(1) A written consent document that em-

bodies the elements of informed consent

required by §46.116. This form may be read

to the subject or the subject's legally author-

ized representative, but in any event, the

investigator shall give either the subject or

the representative adequate opportunity to

read it before it is signed; or

(2) A short form written consent document

stating that the elements of informed con-

sent required by §46.116 have been pre-

sented orally to the subject or the subject's

legally authorized representative. When this

method is used, there shall be a witness to

the oral presentation. Also, the IRB shall

approve a written summary of what is to be

said to the subject or the representative.

Only the short form itself is to be signed by

the subject or the representative. However,

the witness shall sign both the short form

and a copy of the summary, and the person

actually obtaining consent shall sign a copy

of the summary. A copy of the summary

shall be given to the subject or the represen-

tative, in addition to a copy of the short

form.

the investigator to obtain a signed consent

form for some or all subjects if it finds ei-

ther:

(1) That the only record linking the subject

and the research would be the consent docu-

ment and the principal risk would be poten-

tial harm resulting from a breach of confi-

dentiality. Each subject will be asked

whether the subject wants documentation

linking the subject with the research, and the

subject's wishes will govern; or

(2) That the research presents no more than

minimal risk of harm to subjects and in-

volves no procedures for which written con-

sent is normally required outside of the re-

search context.

In cases in which the documentation re-

quirement is waived, the IRB may require

the investigator to provide subjects with a

written statement regarding the research.

(Approved by the Office of Management and Budget

under Control Number 0990-0260.)

[56 FR 28012, 28022, June 18, 1991, as amended at 70

FR 36328, June 23, 2005

]

§46.118 Applications and proposals lack-

ing definite plans for involvement of

human subjects.

Certain types of applications for grants, co-

operative agreements, or contracts are sub-

mitted to departments or agencies with the

knowledge that subjects may be involved

within the period of support, but definite

plans would not normally be set forth in the

application or proposal. These include ac-

tivities such as institutional type grants when

selection of specific projects is the institu-

tion's responsibility; research training grants

in which the activities involving subjects

remain to be selected; and projects in which

human subjects' involvement will depend

upon completion of instruments, prior ani-

mal studies, or purification of compounds.

These applications need not be reviewed by

an IRB before an award may be made. How-

ever, except for research exempted or

waived under §46.101(b) or (i), no human

subjects may be involved in any project sup-

ported by these awards until the project has

been reviewed and approved by the IRB, as

provided in this policy, and certification

submitted, by the institution, to the depart-

ment or agency.

8 45 CFR 46

§46.119 Research undertaken without the

intention of involving human sub-

jects.

In the event research is undertaken without

the intention of involving human subjects,

but it is later proposed to involve human

subjects in the research, the research shall

first be reviewed and approved by an IRB,

as provided in this policy, a certification

submitted, by the institution, to the depart-

ment or agency, and final approval given to

the proposed change by the department or

agency.

§46.120 Evaluation and disposition of

applications and proposals for re-

search to be conducted or supported

by a Federal Department or Agency.

(a) The department or agency head will

evaluate all applications and proposals in-

volving human subjects submitted to the

department or agency through such officers

and employees of the department or agency

and such experts and consultants as the de-

partment or agency head determines to be

appropriate. This evaluation will take into

consideration the risks to the subjects, the

adequacy of protection against these risks,

the potential benefits of the research to the

subjects and others, and the importance of

the knowledge gained or to be gained.

(b) On the basis of this evaluation, the de-

partment or agency head may approve or

disapprove the application or proposal, or

enter into negotiations to develop an ap-

provable one.

§46.121 [Reserved]

§46.122 Use of Federal funds.

Federal funds administered by a department

or agency may not be expended for research

involving human subjects unless the require-

ments of this policy have been satisfied.

§46.123 Early termination of research sup-

port: Evaluation of applications and propos-

als.

(a) The department or agency head may

require that department or agency support

for any project be terminated or suspended

in the manner prescribed in applicable pro-

gram requirements, when the department or

agency head finds an institution has materi-

ally failed to comply with the terms of this

policy.

(b) In making decisions about supporting or

approving applications or proposals covered

by this policy the department or agency head

may take into account, in addition to all

other eligibility requirements and program

criteria, factors such as whether the appli-

cant has been subject to a termination or

suspension under paragraph (a) of this sec-

tion and whether the applicant or the person

or persons who would direct or has/have

directed the scientific and technical aspects

of an activity has/have, in the judgment of

the department or agency head, materially

failed to discharge responsibility for the pro-

tection of the rights and welfare of human

subjects (whether or not the research was

subject to federal regulation).

§46.124 Conditions.

With respect to any research project or any

class of research projects the department or

agency head may impose additional condi-

tions prior to or at the time of approval

when in the judgment of the department or

agency head additional conditions are neces-

sary for the protection of human subjects.

Subpart B

Additional Protections for Preg-

nant Women, Human Fetuses

and Neonates Involved in Re-

Source: 66 FR 56778, Nov. 13, 2001, unless otherwise

noted.

§46.201 To what do these regulations

apply?

(a) Except as provided in paragraph (b) of

this section, this subpart applies to all re-

search involving pregnant women, human

fetuses, neonates of uncertain viability, or

nonviable neonates conducted or supported

by the Department of Health and Human

Services (DHHS). This includes all research

conducted in DHHS facilities by any person

and all research conducted in any facility by

DHHS employees.

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

(6) are applicable to this subpart.

are applicable to this subpart. Reference to

State or local laws in this subpart and in

§46.101(f) is intended to include the laws of

federally recognized American Indian and

Alaska Native Tribal Governments.

(d) The requirements of this subpart are in

addition to those imposed under the other

subparts of this part.

§46.202 Definitions.

The definitions in §46.102 shall be applica-

ble to this subpart as well. In addition, as

used in this subpart:

(a) Dead fetus means a fetus that exhibits

neither heartbeat, spontaneous respiratory

activity, spontaneous movement of volun-

tary muscles, nor pulsation of the umbilical

cord.

(b) Delivery means complete separation of

the fetus from the woman by expulsion or

extraction or any other means.

from implantation until delivery.

(d) Neonate means a newborn.

(e) Nonviable neonate means a neonate after

delivery that, although living, is not viable.

(f) Pregnancy encompasses the period of

time from implantation until delivery. A

woman shall be assumed to be pregnant if

she exhibits any of the pertinent presump-

tive signs of pregnancy, such as missed men-

ses, until the results of a pregnancy test are

negative or until delivery.

(g) Secretary means the Secretary of Health

and Human Services and any other officer

or employee of the Department of Health

and Human Services to whom authority has

been delegated.

(h) Viable, as it pertains to the neonate,

means being able, after delivery, to survive

(given the benefit of available medical ther-

apy) to the point of independently maintain-

ing heartbeat and respiration. The Secretary

may from time to time, taking into account

medical advances, publish in the FEDERAL

ing 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 ex-

tent permitted and in accordance with the

requirements of subparts A and D of this

part.

§46.203 Duties of IRBs in connection

with research involving pregnant

women, fetuses, and neonates.

In addition to other responsibilities assigned

to IRBs under this part, each IRB shall re-

view research covered by this subpart and

approve only research which satisfies the

conditions of all applicable sections of this

subpart and the other subparts of this part.

§46.204 Research involving pregnant

women or fetuses.

Pregnant women or fetuses may be involved

in research if all of the following conditions

are met:

(a) Where scientifically appropriate, preclini-

cal studies, including studies on pregnant

animals, and clinical studies, including stud-

ies on nonpregnant women, have been con-

ducted and provide data for assessing poten-

tial risks to pregnant women and fetuses;

45 CFR 46 9

(b) The risk to the fetus is caused solely by

interventions or procedures that hold out

the prospect of direct benefit for the woman

or the fetus; or, if there is no such prospect

of benefit, the risk to the fetus is not greater

than minimal and the purpose of the re-

search is the development of important bio-

medical knowledge which cannot be ob-

tained by any other means;

ing the objectives of the research;

(d) If the research holds out the prospect of

direct benefit to the pregnant woman, the

prospect of a direct benefit both to the preg-

nant 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 devel-

opment of important biomedical knowledge

that cannot be obtained by any other means,

her consent is obtained in accord with the

informed consent provisions of subpart A

of this part;

(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 in-

formed consent provisions of subpart A of

this part, except that the father's consent

need not be obtained if he is unable to con-

sent because of unavailability, incompetence,

or temporary incapacity or the pregnancy

resulted from rape or incest.

(f) Each individual providing consent under

paragraph (d) or (e) of this section is fully

informed regarding the reasonably foresee-

able impact of the research on the fetus or

neonate;

(g) For children as defined in §46.402(a)

who are pregnant, assent and permission are

obtained in accord with the provisions of

subpart D of this part;

(h) No inducements, monetary or otherwise,

will be offered to terminate a pregnancy;

(i) Individuals engaged in the research will

have no part in any decisions as to the tim-

ing, method, or procedures used to termi-

nate a pregnancy; and

(j) Individuals engaged in the research will

have no part in determining the viability of a

neonate.

§46.205 Research involving neonates.

(a) Neonates of uncertain viability and non-

viable neonates may be involved in research

if all of the following conditions are met:

(1) Where scientifically appropriate, pre-

clinical and clinical studies have been con-

ducted and provide data for assessing po-

tential risks to neonates.

(2) Each individual providing consent un-

der paragraph (b)(2) or (c)(5) of this sec-

tion is fully informed regarding the rea-

sonably foreseeable impact of the research

on the neonate.

(3) Individuals engaged in the research will

have no part in determining the viability of

a neonate.

(4) The requirements of paragraph (b) or

cable.

(b) Neonates of uncertain viability. Until it

has been ascertained whether or not a neo-

nate is viable, a neonate may not be involved

in research covered by this subpart unless

the following additional conditions have

been met:

(1) The IRB determines that:

(i) The research holds out the prospect of

enhancing the probability of survival of

the neonate to the point of viability, and

any risk is the least possible for achieving

that objective, or

(ii) The purpose of the research is the de-

velopment of important biomedical

knowledge which cannot be obtained by

other means and there will be no added

risk to the neonate resulting from the re-

search; and

(2) The legally effective informed consent

of eith

er parent of the n

eonate or, if nei-

ther parent is able to consent because of

unavailability, incompetence, or temporary

incapacity, the legally effective informed

consent of either parent's legally author-

ized representative is obtained in accord

with subpart A of this part, except that the

consent of the father or his legally author-

ized representative need not be obtained if

the pregnancy resulted from rape or incest.

viable neonate may not be involved in re-

search covered by this subpart unless all of

the following additional conditions are met:

(1) Vital functions of the neonate will not

be artificially maintained;

(2) The research will not terminate the

heartbeat or respiration of the neonate;

(3) There will be no added risk to the neo-

nate resulting from the research;

(4) The purpose of the research is the de-

velopment of important biomedical

knowledge that cannot be obtained by

other means; and

(5) The legally effective informed consent

of both parents of the neonate is obtained

in accord with subpart A of this part, ex-

cept that the waiver and alteration provi-

sions of §46.116(c) and (d) do not apply.

However, if either parent is unable to con-

sent because of unavailability, incompe-

tence, or temporary incapacity, the in-

formed consent of one parent of a nonvi-

able neonate will suffice to meet the re-

quirements 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 deliv-

ery, that has been determined to be viable

may be included in research only to the ex-

tent permitted by and in accord with the

requirements of subparts A and D of this

part.

§46.206 Research involving, after deliv-

ery, the placenta, the dead fetus or

fetal material.

(a) Research involving, after delivery, the

placenta; the dead fetus; macerated fetal

material; or cells, tissue, or organs excised

from a dead fetus, shall be conducted only

in accord with any applicable federal, state,

or local laws and regulations regarding such

activities.

(b) If information associated with material

described in paragraph (a) of this section is

recorded for research purposes in a manner

that living individuals can be identified, di-

rectly or through identifiers linked to those

individuals, those individuals are research

subjects and all pertinent subparts of this

part are applicable.

§46.207 Research not otherwise approv-

able which presents an opportunity

to understand, prevent, or alleviate a

serious problem affecting the health

or welfare of pregnant women, fe-

tuses, or neonates.

The Secretary will conduct or fund research

that the IRB does not believe meets the

requirements of §46.204 or §46.205 only if:

(a) The IRB finds that the research presents

10 45 CFR 46

a reasonable opportunity to further the un-

derstanding, prevention, or alleviation of a

serious problem affecting the health or wel-

fare of pregnant women, fetuses or neo-

nates; and

(b) The Secretary, after consultation with a

panel of experts in pertinent disciplines (for

example: science, medicine, ethics, law) and

following opportunity for public review and

comment, including a public meeting an-

nounced in the FEDERAL REGISTER, has

determined either:

(1) That the research in fact satisfies the

conditions of §46.204, as applicable; or

(2) The following:

(i) The research presents a reasonable op-

portunity to further the understanding,

prevention, or alleviation of a serious

problem affecting the health or welfare of

pregnant women, fetuses or neonates;

(ii) The research will be conducted in ac-

cord with sound ethical principles; and

(iii) Informed consent will be obtained in

accord with the informed consent provi-

sions of subpart A and other applicable

subparts of this part.

Subpart C

Additional Protections Pertaining

to Biomedical and Behavioral Re-

search Involving Prisoners as

Subjects

Source: 43 FR 53655, Nov. 16, 1978, unless otherwise

noted.

§46.301 Applicability.

(a) The regulations in this subpart are appli-

cable to all biomedical and behavioral re-

search conducted or supported by the De-

partment of Health and Human Services

involving prisoners as subjects.

(b) Nothing in this subpart shall be con-

strued as indicating that compliance with the

procedures set forth herein will authorize

research involving prisoners as subjects, to

the extent such research is limited or barred

by applicable State or local law.

addition to those imposed under the other

subparts of this part.

§46.302 Purpose.

Inasmuch as prisoners may be under con-

straints because of their incarceration which

could affect their ability to make a truly vol-

untary and uncoerced decision whether or

not to participate as subjects in research, it is

the purpose of this subpart to provide addi-

tional safeguards for the protection of pris-

oners involved in activities to which this

subpart is applicable.

§46.303 Definitions.

As used in this subpart:

(a) Secretary means the Secretary of Health

and Human Services and any other officer

or employee of the Department of Health

and Human Services to whom authority has

been delegated.

(b) DHHS means the Department of Health

and Human Services.

ily confined or detained in a penal institu-

tion. The term is intended to encompass

individuals sentenced to such an institution

under a criminal or civil statute, individuals

detained in other facilities by virtue of stat-

utes or commitment procedures which pro-

vide alternatives to criminal prosecution or

incarceration in a penal institution, and indi-

viduals detained pending arraignment, trial,

or sentencing.

(d) Minimal risk is the probability and magni-

tude of physical or psychological harm that

is normally encountered in the daily lives, or

in the routine medical, dental, or psychologi-

cal examination of healthy persons.

§46.304 Composition of Institutional

Review Boards where prisoners are

involved.

In addition to satisfying the requirements in

§46.107 of this part, an Institutional Review

Board, carrying out responsibilities under

this part with respect to research covered by

this subpart, shall also meet the following

specific requirements:

(a) A majority of the Board (exclusive of

prisoner members) shall have no association

with the prison(s) involved, apart from their

membership on the Board.

(b) At least one member of the Board shall

be a prisoner, or a prisoner representative

with appropriate background and experience

to serve in that capacity, except that where a

particular research project is reviewed by

more than one Board only one Board need

satisfy this requirement.

[

43 FR 53655, Nov. 16, 1978, as amended at 46 FR

8366, Jan. 26, 1981]

§46.305 Additional duties of the Institu-

tional Review Boards where prison-

ers are involved.

(a) In addition to all other responsibilities

prescribed for Institutional Review Boards

under this part, the Board shall review re-

search covered by this subpart and approve

such research only if it finds that:

(1) The research under review represents

one of the categories of research permissi-

ble under §46.306(a)(2);

(2) Any possible advantages accruing to

the prisoner through his or her participa-

tion in the research, when compared to the

general living conditions, medical care,

quality of food, amenities and opportunity

for earnings in the prison, are not of such

a magnitude that his or her ability to weigh

the risks of the research against the value

of such advantages in the limited choice

environment of the prison is impaired;

(3) The risks involved in the research are

commensurate with risks that would be

accepted by nonprisoner volunteers;

(4) Procedures for the selection of subjects

within the prison are fair to all prisoners

and immune from arbitrary intervention

by prison authorities or prisoners. Unless

the principal investigator provides to the

Board justification in writing for following

some other procedures, control subjects

must be selected randomly from the group

of available prisoners who meet the char-

acteristics needed for that particular re-

search project;

(5) The information is presented in lan-

guage which is understandable to the sub-

ject population;

(6) Adequate assurance exists that parole

boards will not take into account a pris-

oner's participation in the research in mak-

ing decisions regarding parole, and each

prisoner is clearly informed in advance

that participation in the research will have

no effect on his or her parole; and

(7) Where the Board finds there may be a

need for follow-up examination or care of

participants after the end of their partici-

pation, adequate provision has been made

for such examination or care, taking into

account the varying lengths of individual

prisoners' sentences, and for informing

participants of this fact.

(b) The Board shall carry out such other

duties as may be assigned by the Secretary.

45 CFR 46 11

tary, in such form and manner as the Secre-

tary may require, that the duties of the

Board under this section have been fulfilled.

§46.306 Permitted research involving

prisoners.

(a) Biomedical or behavioral research con-

ducted or supported by DHHS may involve

prisoners as subjects only if:

(1) The institution responsible for the con-

duct of the research has certified to the

Secretary that the Institutional Review

Board has approved the research under

§46.305 of this subpart; and

(2) In the judgment of the Secretary the

proposed research involves solely the fol-

lowing:

(i) Study of the possible causes, effects,

and processes of incarceration, and of

criminal behavior, provided that the study

presents no more than minimal risk and

no more than inconvenience to the sub-

jects;

(ii) Study of prisons as institutional struc-

tures or of prisoners as incarcerated per-

sons, provided that the study presents no

more than minimal risk and no more than

inconvenience to the subjects;

(iii) Research on conditions particularly

affecting prisoners as a class (for example,

vaccine trials and other research on hepati-

tis which is much more prevalent in pris-

ons than elsewhere; and research on social

and psychological problems such as alco-

holism, drug addiction, and sexual as-

saults) provided that the study may pro-

ceed only after the Secretary has consulted

with appropriate experts including experts

in penology, medicine, and ethics, and

published notice, in the FEDERAL REG-

ISTER, of his intent to approve such re-

search; or

(iv) Research on practices, both innovative

and accepted, which have the intent and

reasonable probability of improving the

health or well-being of the subject. In

cases in which those studies require the

assignment of prisoners in a manner con-

sistent with protocols approved by the

IRB to control groups which may not

benefit from the research, the study may

proceed only after the Secretary has con-

sulted with appropriate experts, including

experts in penology, medicine, and ethics,

and published notice, in the FEDERAL

research.

(b) Except as provided in paragraph (a) of

this section, biomedical or behavioral re-

search conducted or supported by DHHS

shall not involve prisoners as subjects.

Subpart D

Additional Protections for Chil-

dren Involved as Subjects in Re-

Source: 48 FR 9818, March 8, 1983, unless otherwise

noted.

§46.401 To what do these regulations

apply?

(a) This subpart applies to all research in-

volving 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 De-

partment may adopt such nonsubstantive,

procedural modifications as may be appro-

priate 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 paragraph (i) of

§46.101 of subpart A, waive the applicabil-

ity of some or all of the requirements of

these regulations for research of this type.

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

through (b)(6) are applicable to this subpart.

The exemption at §46.101(b)(2) regarding

educational tests is also applicable to this

subpart. However, the exemption at §46.101

(b)(2) for research involving survey or inter-

view procedures or observations of public

behavior does not apply to research covered

by this subpart, except for research involv-

ing observation of public behavior when the

investigator(s) do not participate in the ac-

tivities being observed.

for waiver as they appear in paragraphs (c)

through (i) of §46.101 of subpart A are ap-

plicable to this subpart.

[48 FR 9818, Mar.8, 1983; 56 FR 28032, June 18, 1991;

56 FR 29757, June 28, 1991.]

§46.402 Definitions.

The definitions in §46.102 of subpart A shall

be applicable to this subpart as well. In addi-

tion, as used in this subpart:

(a) Children are persons who have not at-

tained the legal age for consent to treat-

ments or procedures involved in the re-

search, under the applicable law of the juris-

diction in which the research will be con-

ducted.

(b) Assent means a child's affirmative agree-

ment to participate in research. Mere failure

to object should not, absent affirmative

agreement, be construed as assent.

(s) or guardian to the participation of their

child or ward in research.

(d) Parent means a child's biological or adop-

tive parent.

(e) Guardian means an individual who is au-

thorized under applicable State or local law

to consent on behalf of a child to general

medical care.

§46.403 IRB duties.

In addition to other responsibilities assigned

to IRBs under this part, each IRB shall re-

view research covered by this subpart and

approve only research which satisfies the

conditions of all applicable sections of this

subpart.

§46.404 Research not involving greater

than minimal risk.

HHS will conduct or fund research in which

the IRB finds that no greater than minimal

risk to children is presented, only if the IRB

finds that adequate provisions are made for

soliciting the assent of the children and the

permission of their parents or guardians, as

set forth in §46.408.

§46.405 Research involving greater than

minimal risk but presenting the

prospect of direct benefit to the indi-

vidual subjects.

HHS will conduct or fund research in which

the IRB finds that more than minimal risk to

children is presented by an intervention or

procedure that holds out the prospect of

direct benefit for the individual subject, or

by a monitoring procedure that is likely to

contribute to the subject's well-being, only if

the IRB finds that:

(a) The risk is justified by the anticipated

benefit to the subjects;

(b) The relation of the anticipated benefit to

the risk is at least as favorable to the subjects

as that presented by available alternative

approaches; and

ing the assent of the children and permission

of their parents or guardians, as set forth in

§46.408.

12 45 CFR 46

§46.406 Research involving greater than

minimal risk and no prospect of di-

rect benefit to individual subjects,

but likely to yield generalizable

knowledge about the subject's disor-

der or condition.

HHS will conduct or fund research in which

the IRB finds that more than minimal risk to

children is presented by an intervention or

procedure that does not hold out the pros-

pect of direct benefit for the individual sub-

ject, or by a monitoring procedure which is

not likely to contribute to the well-being of

the subject, only if the IRB finds that:

(a) The risk represents a minor increase over

minimal risk;

(b) The intervention or procedure presents

experiences to subjects that are reasonably

commensurate with those inherent in their

actual or expected medical, dental, psycho-

logical, social, or educational situations;

yield generalizable knowledge about the

subjects' disorder or condition which is of

vital importance for the understanding or

amelioration of the subjects' disorder or

condition; and

(d) Adequate provisions are made for solicit-

ing assent of the children and permission of

their parents or guardians, as set forth in

§46.408.

§46.407 Research not otherwise approv-

able which presents an opportunity

to understand, prevent, or alleviate a

serious problem affecting the health

or welfare of children.

HHS will conduct or fund research that the

IRB does not believe meets the require-

ments of §46.404, §46.405, or §46.406 only

if:

(a) the IRB finds that the research presents a

reasonable opportunity to further the under-

standing, prevention, or alleviation of a seri-

ous problem affecting the health or welfare

of children; and

(b) the Secretary, after consultation with a

panel of experts in pertinent disciplines (for

example: science, medicine, education, eth-

ics, law) and following opportunity for pub-

lic review and comment, has determined

either:

(1) that the research in fact satisfies the con-

ditions of §46.404, §46.405, or §46.406, as

applicable, or (2) the following:

(i) the research presents a reasonable oppor-

tunity to further the understanding, preven-

tion, or alleviation of a serious problem af-

fecting the health or welfare of children;

(ii) the research will be conducted in accor-

dance with sound ethical principles;

(iii) adequate provisions are made for solicit-

ing the assent of children and the permission

of their parents or guardians, as set forth in

§46.408.

§46.408 Requirements for permission by

parents or guardians and for assent

by children.

(a) In addition to the determinations re-

quired 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 judg-

ment 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 in-

volved. 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 deter-

mines that the capability of some or all of

the children is so limited that they cannot

reasonably be consulted or that the interven-

tion 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

search, the assent of the children is

not a necessary condition for proceeding

with the research. Even where the IRB de-

termines 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 Subpart A.

(b) In addition to the determinations re-

quired under other applicable sections of

this subpart, the IRB shall determine, in

accordance with and to the extent that con-

sent is required by §46.116 of Subpart A,

that adequate provisions are made for solic-

iting the permission of each child's parents

or guardian. Where parental permission is to

be obtained, the IRB may find that the per-

mission of one parent is sufficient for re-

search 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 par-

ent has legal responsibility for the care and

custody of the child.

contained in §46.116 of subpart A, if the

IRB determines that a research 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 (for example, ne-

glected or abused children), it may waive the

consent requirements in Subpart A of this

part and paragraph (b) of this section, pro-

vided an appropriate mechanism for pro-

tecting the children who will participate as

subjects in the research is substituted, and

provided further that the waiver is not in-

consistent 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 re-

search 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 subpart A.

(e) When the IRB determines that assent is

required, it shall also determine whether and

how assent must be documented.

§46.409 Wards.

(a) Children who are wards of the state or

any other agency, institution, or entity can

be included in research approved under

§46.406 or §46.407 only if such research is:

(1) Related to their status as wards; or

(2) Conducted in schools, camps, hospi-

tals, institutions, or similar settings in

which the majority of children involved as

subjects are not wards.

(b) If the research is approved under para-

graph (a) of this section, the IRB shall re-

quire appointment of an advocate for each

child who is a ward, in addition to any other

individual acting on behalf of the child as

guardian or in loco parentis. One individual

may serve as advocate for more than one

child. The advocate shall be an individual

who has the background and experience to

act in, and agrees to act in, the best interests

of the child for the duration of the child's

participation in the research and who is not

associated in any way (except in the role as

advocate or member of the IRB) with the

research, the investigator(s), or the guardian

organization.

45 CFR 46 13

14 45 CFR 46

Subpart E

Registration of Institutional Re-

view Boards

Source: 74 FR 2399, January 15, 2009, unless otherwise

noted.

§46.501 What IRBs must be registered?

Each IRB that is designated by an institution

under an assurance of compliance approved

for federalwide use by the Office for Human

Research Protections (OHRP) under

§46.103(a) and that reviews research involv-

ing human subjects conducted or supported

by the Department of Health and Human

Services (HHS) must be registered with

HHS. An individual authorized to act on

behalf of the institution or organization op-

erating the IRB must submit the registration

information.

§46.502 What information must be pro-

vided when registering an IRB?

The following information must be pro-

vided to HHS when registering an IRB:

(a) The name, mailing address, and street

address (if different from the mailing ad-

dress) of the institution or organization op-

erating the IRB(s); and the name, mailing

address, phone number, facsimile number,

and electronic mail address of the senior

officer or head official of that institution or

organization who is responsible for oversee-

ing activities performed by the IRB.

(b) The name, mailing address, phone num-

ber, facsimile number, and electronic mail

address of the contact person providing the

registration information.

the institution or organization, and the IRB's

mailing address, street address (if different

from the mailing address), phone number,

facsimile number, and electronic mail ad-

dress.

(d) The name, phone number, and electronic

mail address of the IRB chairperson.

(e)(1) The approximate numbers of:

(i) All active protocols; and

(ii) Active protocols conducted or sup-

ported by HHS.

(2) For purpose of this regulation, an

``active protocol'' is any protocol for

which the IRB conducted an initial review

or a continuing review at a convened

meeting or under an expedited review

procedure during the preceding twelve

months.

(f) The approximate number of full-time

equivalent positions devoted to the IRB's

administrative activities.

§46.503 When must an IRB be regis-

tered?

An IRB must be registered before it can be

designated under an assurance approved for

federalwide use by OHRP under §46.103(a).

IRB registration becomes effective when

reviewed and accepted by OHRP.

The registration will be effective for 3 years.

§46.504 How must an IRB be regis-

tered?

Each IRB must be registered electronically

through http://ohrp.cit.nih.gov/efile unless

an institution or organization lacks the abil-

ity to register its IRB(s) electronically. If an

institution or organization lacks the ability to

its IRB registration information in writing to

OHRP.

§46.505 When must IRB registration

information be renewed or updated?

(a) Each IRB must renew its registration

every 3 years.

(b) The registration information for an IRB

must be updated within 90 days after

changes occur regarding the contact person

who provided the IRB registration informa-

tion or the IRB chairperson. The updated

registration information must be submitted

in accordance with §46.504.

to, and accepted by, OHRP begins a new 3-

year effective period.

(d) An institution's or organization's deci-

sion to disband a registered IRB which it is

operating also must be reported to OHRP in

writing within 30 days after permanent ces-

sation of the IRB's review of HHS-

conducted or -supported research.