PART 46—PROTECTION OF HUMAN SUBJECTS
Subpart A—Basic HHS Policy for Protection
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 Department or Agency.
46.104–46.106 [Reserved]
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 research.
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 informed
consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking
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 research to be
conducted or supported by a Federal Department
or Agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support:
Evaluation of applications and proposals.
46.124 Conditions.
Subpart B—Additional Protections Pertaining
to Research, Development,
and Related Activities Involving
Fetuses, Pregnant Women, and Human
In Vitro Fertilization
46.201 Applicability.
46.202 Purpose.
46.203 Definitions.
46.204 Ethical Advisory Boards.
46.205 Additional duties of the Institutional
Review Boards in connection with activities
involving fetuses, pregnant women,
or human in vitro fertilization.
46.206 General limitations.
46.207 Activities directed toward pregnant
women as subjects.
46.208 Activities directed toward fetuses in
utero as subjects.
46.209 Activities directed toward fetuses ex
utero, including nonviable fetuses, as
subjects.
46.210 Activities involving the dead fetus,
fetal material, or the placenta.
46.211 Modification or waiver of specific requirements.
Subpart C—Additional Protections Pertaining
to Biomedical and Behavioral
Research Involving Prisoners as Subjects
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 Institutional
Review Boards where prisoners are involved.
46.306 Permitted research involving prisoners.
Subpart D—Additional Protections for
Children Involved as Subjects in Research
46.401 To what do these regulations apply?
46.402 Definitions.
46.403 IRB duties.
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105
Department of Health and Human Services § 46.101
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 prospect of direct
benefit to individual subjects, but likely
to yield generalizable knowledge about
the subject’s disorder or condition.
46.407 Research not otherwise approvable
which presents an opportunity 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.
EFFECTIVE DATE NOTE: At 66 FR 3882, Jan.
17, 2001, the authority for part 46 was revised,
effective Mar. 19, 2001. At 66 FR 15352, Mar.
19, 2001, the effective date was delayed until
May 18, 2001, and at 66 FR 27599, May 18, 2001,
the effective date was further delayed until
Nov. 14, 2001. For the convenience of the
user, the revised text is set forth as follows:
AUTHORITY: 5 U.S.C. 301; 42 U.S.C. 289(a).
EDITORIAL NOTE: The Department of
Health and Human Services issued a notice
of waiver regarding the requirements 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 information see 47 FR
9208, Mar. 4, 1982.
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, supported 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 conducted,
supported, or otherwise subject
to regulation by the federal government
outside the United States.

(1) Research that is conducted or supported
by a federal department or
agencyor agency, whether or not it is regulated
as 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 defined 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 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 categories 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 techniques, curricula,
or classroom management
methods.

(2) Research involving the use of educational
tests (cognitive, diagnostic,
aptitude, achievement), survey procedures,
interview procedures or observation
of public behavior, unless:

(i) Information obtained is recorded
in such a manner that human subjects
can be identified, directly or through
identifiers linked to the subjects; and

(ii) any disclosure of the human subjects’
responses outside the research
could reasonably place the subjects at
risk of criminal or civil liability or be
damaging to the subjects’ financial
standing, employability, or reputation.

(3) Research involving the use of educational
tests (cognitive, diagnostic,
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106
§ 46.101 45 CFR Subtitle A (10–1–01 Edition)
aptitude, achievement), survey procedures,
interview procedures, or observation
of public behavior that is not
exempt under paragraph (b)(2) of this
section, if:

(i) The human subjects are elected or
appointed public officials or candidates
for public office; or

(ii) federal statute(
s) require(s) without exception that
the confidentiality of the personally
identifiable information will be maintained
throughout the research and
thereafter.

(4) Research, involving the collection
or study of existing data, documents,
records, pathological specimens, or diagnostic
specimensdiagnostic 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 subject
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 obtaining
benefits or services under those programs;

(iii) possible changes in or alternatives
to those programs or procedures; oror

(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
wholesome foods without additives are
consumed 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 Administration or approved
by the Environmental Protection
Agency or the Food Safety and Inspection
Service of the U.S. Department of
Agriculture.

(c) Department or agency heads retain
final 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 department or
agency but not otherwise covered 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 protections for human subjects.

(f) This policy does not affect any
state or local laws or regulations which
may otherwise be applicable and which
provide additional 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 Medical Assembly Declaration
(Declaration of Helsinki amended 1989)
issued either by sovereign states or by
an organization whose function for the
protection of human research subjects
is internationally recognized.] In these
circumstances, if a department or
agency head determines that the procedures
prescribed by the institution afford
protections 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 procedural
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 REGISTER or will
be otherwise published as provided in
department or agency procedures.

(i) Unless otherwise required by law,
department or agency heads may waive
the applicability of some or all of the
provisions of this policy to specific research
activities or classes of research
activities otherwise covered 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
Office for Protection from Research
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107
Research Risks, Department of Health and Human Services § 46.102
1 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 incorporated
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,
fetuses, pregnant women, or human in vitro
fertilization, subparts B and 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.
Risks, Department of Health and
Human Services (HHS), and shall also
(HHS), and shall also publish them in the FEDERAL REGISTER
or in such other manner as provided in
department or agency procedures.1

[56 FR 28012, 28022, June 18, 1991; 56 FR 29756,
June 28, 1991]

§ 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 delegated.

(b) Institution means any public or
private entity or agency (including federal,
state, and other agencies).

(c) Legally authorized representative
means an individual or judicial or
other body authorized under applicable
law to consent on behalf of a prospective
subject to the subject’s participation
in the procedure(s) involved in the
research.

(d) Research means a systematic investigation,
including research development,
testing and evaluation, designed
to develop or contribute to generalizable
knowledge. Activities which
meet this definition constitute research
for purposes of this policy,
whether or not they are conducted or
supported under a program which is
considered research for other purposes.
For example, some demonstration and
service programs may include research
activities.

(e) Research subject to regulation, and
similar terms are intended to encompass
those research activities for which
a federal department or agency has
specific responsibility for regulating as
a research activity, (for example, Investigational
New Drug requirements
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 requirements administered
by the Department of Labor).

(f) Human subject means a living individual
about whom an investigator
(whether professional or student) conducting
research obtains

(1) Data through intervention or
interaction with the individual, or

(2) Identifiable private information.
Intervention includes both physical procedures
by which data are gathered (for
examplefor example, venipuncture) and manipulations
of the subject or the subject’s environment
that are performed for research
purposes. Interaction includes
communication or interpersonal contact
between investigator and subject.
Private information includes information
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 provided for specific
purposes by an individual and
which and which the individual can reasonably
expect will not be made public (for example,
a medical record). Private information
must be individually identifiable
(i.e., the identity of the subject is
or may readily be ascertained by the
investigator or associated with the information)
in order for obtaining the
information to constitute research involving
human subjects.

(g) IRB means an institutional review
board established in accord with and
for the purposes 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 the constraints set forth by the IRB and by
other institutional and federal requirements.
(i) Minimal risk means that the probability
and magnitude of harm or discomfort
anticipated in the research are
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(i) Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are Frm 00107 Fmt 8010 Sfmt 8010 Y:\SGML\194175T.XXX pfrm07 PsN: 194175T
108
§ 46.103 45 CFR Subtitle A (10–1–01 Edition)
not greater in and of themselves than
those ordinarily encountered in daily
life or during the performance of routine
physical or psychological examinations
or tests.

(j) Certification means the official notification
by notification by the institution to the supporting
department or agency, in accordance
with the requirements of this
policy, that a research project or activity
involving human subjects has been
reviewed and approved by an IRB in accordance
with an approved assurance.

§ 46.103 Assuring compliance with this

...

policy—research conducted or supported

...

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 department or agency shall
provide shall provide written assurance satisfactory
to 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
Protection from Research Risks, HHS,
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,
reports (except certification)
required by this policy to be made to
department and agency heads shall
also be made to the Office for Protection
from Research Risks, HHS.

(b) Departments and agencies will
conduct or support research covered by
this policy only if the institution has
an assurance approved as provided in
this in this section, and only if the institution
has certified to the department or
agency head that the research has been
reviewed and approved by an IRB provided
for in the assurance, and will be
subject be subject to continuing review by the
IRB. Assurances applicable to federally
supported or conducted research shall
at a minimum include:

(1) A statement of principles governing
the institution in the discharge
of its responsibilities for protecting the
rights and welfare of human subjects of
research of research conducted at or sponsored by
the institution, regardless of whether
the research is subject to federal regulation.
This may include an appropriate
existing code, declaration, or
statement of ethical principles, or a
statement formulated by the institution
itself. This requirement does not
preempt provisions of this policy applicable
to department- or agency-supported
or regulated research and need
not be applicable to any research exempted
or waived under § 46.101 (b) or
(i).

(2) Designation of one or more IRBs
established 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 recordkeeping duties.

(3) A list of IRB members identified
by name; earned degrees; representative
capacity; indications of experience
such experience such as board certifications, licenses,
etc., sufficient to describe each member’s
chief anticipated contributions to
IRB deliberations; and any employment
or other relationship between
each member and the institution; for
example: full-time employee, part-time
employee, member of governing panel
or board, stockholder, paid or unpaid
consultant. Changes in IRB membership
shall be reported to the department
or agency head, unless in accord
with § 46.103(a) of this policy, the existence
of an HHS-approved assurance is
accepted. In this case, change in IRB
membership shall be reported to the
Office for Protection from Research
Risks, HHS.

(4) Written procedures which the IRB
will follow

(i) for conducting its initial
and continuing review of research and
for reporting its findings and actions to
the investigator and the institution;

(ii) for determining which projects require
review more often than annually
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
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109
Department of Health and Human Services § 46.107
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 noncompliance with this
policy or the requirements or determinations
of the IRB and (ii) any suspension
or termination of IRB approval.

(c) The assurance shall be executed
by an individual authorized to act for
the institution and to assume on behalf
of the institution 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 accordance 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 department
or agency head’s evaluation will
take 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 proposed initial
and continuing review procedures
in procedures in light of the probable risks, and the
size and complexity of the institution.

(e) On the basis of this evaluation,
the department or agency head may
approve or disapprove the assurance, or
enter into negotiations to develop an
approvable one. The department or
agency head may limit the period during
which any particular approved assurance
or class of approved assurances
shall assurances shall remain effective or otherwise
condition or restrict approval.

(f) Certification is required when the
research is supported by a federal department
or agency and not otherwise
exempted or waived under § 46.101 (b) or

(i). An institution with an approved assurance
shall certify that each application
or proposal for research 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 submitted. Under no condition shall
research covered 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 certification is not submitted
within these time limits, the
application or proposal may be returned
to the institution.

(Approved by the Office of Management and
Budget under control number 9999–0020)

[56 FR 28012, 28022, June 18, 1991; 56 FR 29756,
June 28, 1991]

§§ 46.104—46.106 [Reserved]

§ 46.107 IRB membership.

(a) Each IRB shall have at least five
members, with varying backgrounds to
promote complete and adequate review
of research activities commonly conducted
by the institution. The IRB
shall be sufficiently qualified through
the experience and expertise of its
members, and the diversity of the
members, including consideration of
race, gender, and cultural backgrounds
and sensitivity to such issues as community
attitudes, to promote respect
for its advice and counsel in safeguarding
the rights and welfare of
human subjects. In addition to possessing
the professional competence
necessary to review specific research
activities, the IRB shall be able to ascertain
the ascertain the acceptability of proposed
research in terms of institutional commitments
and regulations, applicable
law, and standards of professional conduct
and practice. The IRB shall therefore
include persons knowledgeable in
these areas. If an IRB regularly reviews
research that involves a vulnerable
category of subjects, such as children,
prisoners, pregnant women, or handicapped
or mentally disabled persons,
consideration shall be given to the inclusion
of one or more individuals who
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110
§ 46.108 45 CFR Subtitle A (10–1–01 Edition)
are knowledgeable 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 persons 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.

(c) Each IRB shall include at least
one member whose primary concerns
are in scientific areas and at least one
member whose primary concerns are in
nonscientific areas.

(d) Each IRB shall include at least
one member who is not otherwise affiliated
with the institution and who is
not part of the immediate 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 conflicting interest,
except to provide information requested
by the IRB.

(f) An IRB may, in its discretion, invite
individuals with competence in
special areas to assist in the review of
issues which require expertise beyond
or in addition to that available 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
procedure 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 approved,
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 secure approval), or disapprove
all research activities covered
by this policy.

(b) An IRB shall require that information
given to subjects as part of informed
consent is in accordance with
§ 46.116. The IRB may require that information,
in addition to that specifically
mentioned specifically mentioned in § 46.116, be given to
the subjects when in the IRB’s judgment
the information would meaningfully
add meaningfully add to the protection of the rights
and welfare of subjects.

(c) An IRB shall require documentation
of informed consent or may waive
documentation in accordance with
§ 46.117.

(d) An IRB shall notify investigators
and the institution in writing of its decision
to approve or disapprove the proposed
research activity, or of modifications
required to secure IRB approval
of the research activity. If the IRB decides
to disapprove a research activity,
it shall include in its written notification
a statement of the reasons for its
decision 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 intervals 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 research.

(Approved by the Office of Management and
Budget under control number 9999–0020)

§ 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 REGISTER, a list of categories
of research that may be reviewed by
the 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
Secretary, HHS, in the FEDERAL REGISTER.

A copy of the list is available
from the Office for Protection from Research
Risks, National Institutes of
Health, HHS, Bethesda, Maryland
20892.
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111
Department of Health and Human Services § 46.112

(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 procedure the review may be carried out by the
IRB chairperson or by one or more experienced
reviewers 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).

(c) Each IRB which uses an expedited
review 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.

§ 46.111 Criteria for IRB approval of

...

research.

(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.

(2) Risks to subjects are reasonable
in relation to anticipated benefits, if
any, to subjects, and the importance of
the knowledge 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 longrange
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 research and the setting in
which the research will be conducted
and should be particularly cognizant of
the special problems of research involving
vulnerable populations, such as
children, prisoners, pregnant women,
mentally disabled persons, or economically
or educationally disadvantaged
persons.

(4) Informed consent will be sought
from each prospective subject or the
subject’s legally authorized representative,
in accordance 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 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 subjects 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, pregnant 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.
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112

§ 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 associated with unexpected
serious harm to subjects. Any
suspension or termination of approval
shall include a statement of the reasons
for the IRB’s action and shall be
reported promptly to the investigator,
appropriate institutional officials, and
the department or agency head.

(Approved by the Office of Management and
Budget under control number 9999–0020)

§ 46.114 Cooperative research.

Cooperative research projects are
those projects covered by this policy
which involve more than one institution 
In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with this policy. With the approval of the department or agency head, an institution participating in a cooperative project may enter into a joint review arrangement, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort.

...

(Approved by the Office of Management and Budget under control number 9999–0020)

§ 46.117 Documentation of informed consent.

(a) Except as provided in paragraph (c) of this section, informed consent shall be documented by the use of a written consent form approved by the IRB and signed by the subject or the subject’s legally authorized representative. A copy shall be given to the person signing the form.

...

(Approved by the Office of Management and Budget under control number 9999–0020)

§ 46.118 Applications and proposals lacking definite plans for involvement of human subjects.

Certain types of applications for grants, cooperative agreements, or contracts are submitted 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 activities such as institutional type grants when selection of specific projects is the institution’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 animal studies, or purification of compounds. These applications need not be reviewed by an IRB before an award may be made. However, except for research exempted or waived under § 46.101 (b) or (i), no human subjects may be involved in any project supported 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 department or agency.

§ 46.119 Research undertaken without the intention of involving human subjects.

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 department or agency, and final approval given to the proposed change by the department or agency.

...

[40 FR 33528, Aug. 8, 1975, as amended at 43 FR 1759, Jan. 11, 1978; 59 FR 28276, June 1, 1994]

§ 46.205 Additional duties of the Institutional Review Boards in connection with activities involving fetuses, pregnant women, or human in vitro fertilization.

(a) In addition to the responsibilities prescribed for Institutional Review Boards under Subpart A of this part, the applicant’s or offeror’s Board shall, with respect to activities covered by this subpart, carry out the following additional duties:

...

(i) Individuals engaged in the research will have no part in determining the viability of a fetus.

§ 46.205 Research involving fetuses after delivery.

(a) After delivery, fetuses may be involved in research if all of the following conditions are met:

...

(b) If the research is approved under paragraph (a) of this section, the IRB shall require 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 organizationshall 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.

Footnotes

1. 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 incorporated 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, fetuses, pregnant women, or human in vitro fertilization, subparts B and 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.