Code of Federal Regulations - Title 45: Public Welfare and Title 46: Protection of Human Subjects

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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 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.

46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed
consent.

SUBPART B—
Additional Protections for
Pregnant Women, Human Fetuses and Neonates Involved
in Research
Sec.
46.201 To what do these regulations
apply?

46.118 Applications and proposals lack- 46.202 Definitions.
ing definite plans for involvement
46.203 Duties of IRBs in connection
of human subjects.
with research involving pregnant
women, fetuses, and neonates.
46.119 Research undertaken without
46.104- [Reserved]
the intention of involving human
46.106
46.204 Research involving pregnant
subjects.
women or fetuses.
46.107 IRB membership.
46.120 Evaluation and disposition of
applications and proposals for re- 46.205 Research involving neonates.
46.108 IRB functions and operations.
search to be conducted or supported by a Federal Department or 46.206 Research involving, after deliv46.109 IRB review of research.
ery, the placenta, the dead fetus or
Agency.
fetal material.
46.110 Expedited review procedures for 46.121 [Reserved]
certain kinds of research involving
46.207 Research not otherwise approvno more than minimal risk, and for 46.122 Use of Federal funds.
able which presents an opportunity
minor changes in approved reto understand, prevent, or alleviate
search.
a serious problem affecting the
46.123 Early termination of research
health or welfare of pregnant
support: Evaluation of applica46.111 Criteria for IRB approval of
women, fetuses, or neonates.
tions and proposals.
research.
46.124 Conditions.
46.112 Review by institution.
46.113 Suspension or termination of
IRB approval of research.

2

45 CFR 46

SUBPART C—
SUBPART D—
SUBPART E —
Additional Protections
Additional Protections
Registration of Institutional
Pertaining to Biomedical and for Children Involved as Sub- Review Boards
Behavioral Research Involv- jects
ing
in Research
Prisoners as Subjects
Sec.
46.301 Applicability.

Sec.
46.401 To what do these regulations
apply?

46.302 Purpose.

46.402 Definitions.

46.303 Definitions.

46.403 IRB duties.

46.404 Research not involving greater
46.304 Composition of Institutional
than minimal risk.
Review Boards where prisoners
are involved.
46.405 Research involving greater
than minimal risk but presenting
46.305 Additional duties of the Instithe prospect of direct benefit to
tutional Review Boards where
the individual subjects.
prisoners are involved.
46.306 Permitted research involving
prisoners.

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.

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 registered?
46.504 How must an IRB be registered?
46.505 When must IRB registration
information be renewed or updated?

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
(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.

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, 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 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 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 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 educa-

3
tional tests (cognitive, diagnostic, aptitude,
achievement), survey procedures, interview 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 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, 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.

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
(5) Research and demonstration projects
which are conducted by or subject to the function for the protection of human research subjects is internationally recognized.]
approval of department or agency heads,
and which are designed to study, evaluate, In these circumstances, if a department or
or otherwise examine:(i) Public benefit or agency head determines that the procedures
prescribed by the institution afford protecservice programs; (ii) procedures for obtions that are at least equivalent to those
taining benefits or services under those
programs; (iii) possible changes in or alter- provided in this policy, the department or
natives to those programs or procedures; agency head may approve the substitution of
the foreign procedures in lieu of the proceor (iv) possible changes in methods or
levels of payment for benefits or services dural requirements provided in this policy.
Except when otherwise required by statute,
under those programs.
Executive Order, or the department or
(6) Taste and food quality evaluation and
agency head, notices of these actions as they
consumer acceptance studies, (i) if wholeoccur will be published in the FEDERAL
some foods without additives are conREGISTER or will be otherwise published
sumed or (ii) if a food is consumed that
as provided in department or agency procecontains a food ingredient at or below the
dures.
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
(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.

4

45 CFR 46

(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 Human Research Protections, Department of Health and Human Services
(HHS), or any successor office, and shall
also publish them in the FEDERAL REGISTER or in such other manner as provided
in department or agency procedures.1

within the constraints set forth by the IRB
for regulating as a research activity (for exand by other institutional and federal reample, Investigational New Drug requirequirements.
ments administered by the Food and Drug
Administration). It does not include research (i) Minimal risk means that the probability
activities which are incidentally regulated by and magnitude of harm or discomfort anticia federal department or agency solely as part pated in the research are not greater in and
of the department’s or agency’s broader
of themselves than those ordinarily encounresponsibility to regulate certain types of
tered in daily life or during the performance
activities whether research or non-research of routine physical or psychological examiin nature (for example, Wage and Hour re- nations or tests.
quirements administered by the Department
h) When research covered by this policy
of Labor).
takes place in foreign countries, procedures
(f) Human subject means a living individual
normally followed in the foreign countries
about whom an investigator (whether proto protect human subjects may differ from
fessional or student) conducting research
those set forth in this policy. [An example is
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June obtains
a foreign institution which complies with
28, 1991, as amended at 70 FR 36328, June 23, 2005]
(1) Data through intervention or interac- guidelines consistent with the World Medical Assembly Declaration (Declaration of
tion with the individual, or
§46.102 Definitions.
Helsinki amended 1989) issued either by
(2) Identifiable private information.
(a) Department or agency head means the head
sovereign states or by an organization whose
of any federal department or agency and any Intervention includes both physical procedures function for the protection of human reother officer or employee of any department by which data are gathered (for example,
search subjects is internationally recognized.]
or agency to whom authority has been dele- venipuncture) and manipulations of the sub- In these circumstances, if a department or
gated.
ject or the subject’s environment that are
agency head determines that the procedures
performed for research purposes. Interacprescribed by the institution afford protec(b) Institution means any public or private
tions that are at least equivalent to those
entity or agency (including federal, state, and tion includes communication or interpersonal contact between investigator and sub- provided in this policy, the department or
other agencies).
ject. Private information includes informaagency head may approve the substitution of
(c) Legally authorized representative means an
tion about behavior that occurs in a context the foreign procedures in lieu of the proceindividual or judicial or other body authorin which an individual can reasonably expect dural requirements provided in this policy.
ized under applicable law to consent on
Except when otherwise required by statute,
that no observation or recording is taking
behalf of a prospective subject to the subplace, and information which has been pro- Executive Order, or the department or
ject’s participation in the procedure(s) invided for specific purposes by an individual agency head, notices of these actions as they
volved in the research.
occur will be published in the FEDERAL
and which the individual can reasonably
(d) Research means a systematic investigation, expect will not be made public (for example, REGISTER or will be otherwise published
including research development, testing and a medical record).
as provided in department or agency proceevaluation, designed to develop or contribdures.
Private information must be individually identiute to generalizable knowledge. Activities
fiable (i.e., the identity of the subject is or
which meet this definition constitute research for purposes of this policy, whether may readily be ascertained by the investigaor not they are conducted or supported un- tor or associated with the information) in
der a program which is considered research order for obtaining the information to confor other purposes. For example, some dem- stitute research involving human subjects.
onstration and service programs may include (g) IRB means an institutional review board
research activities.
established in accord with and for the purposes expressed in this policy.
(e) Research subject to regulation, and similar
terms are intended to encompass those re(h) IRB approval means the determination of
search activities for which a federal depart- the IRB that the research has been reviewed
ment or agency has specific responsibility
and may be conducted at an institution

1Institutions 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.

45 CFR 46
§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 written assurance 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 HHSapproved 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
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 approved as provided 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 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 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).

5
(3)A list of IRB members identified by
name; earned degrees; representative capacity; indications of 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 Human Research Protections,
HHS, or any successor office.

this purpose as the department or agency
head determines to be appropriate. The department 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 proposed initial and continuing review 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 remain effective or otherwise
condition or restrict approval.

(4)Written procedures which the IRB will (f) Certification is required when the refollow (i) for conducting its initial and
search is supported by a federal department
continuing review of research and for re- or agency and not otherwise exempted or
porting its findings and actions to the in- waived under §46.101(b) or (i). An instituvestigator and the institution; (ii) for deter- tion with an approved assurance shall certify
mining which projects require review more that each application or proposal for reoften than annually and which projects
search covered by the assurance and by
need verification from sources other than
§46.103 of this Policy has been reviewed and
the investigators that no material changes
approved by the IRB. Such certification
have occurred since previous IRB review;
must be submitted with the application or
and (iii) for ensuring prompt reporting to
proposal or by such later date as may be
the IRB of proposed changes in a research
prescribed by the department or agency to
activity, and for ensuring that such
which the application or proposal is submitchanges in approved research, during the
ted. Under no condition shall research covperiod for which IRB approval has already
ered by §46.103 of the Policy be supported
been given, may not be initiated without
prior to receipt of the certification that the
IRB review and approval except when
research has been reviewed and approved by
necessary to eliminate apparent immediate
the IRB. Institutions without an approved
hazards to the subject.
assurance covering the research shall certify
(5)Written procedures for ensuring
within 30 days after receipt of a request for
prompt reporting to the IRB, appropriate such a certification from the department or
institutional officials, and the department agency, that the application or proposal has
or agency head of (i) any unanticipated
been approved by the IRB. If the certificaproblems involving risks to subjects or
tion is not submitted within these time limothers or any serious or continuing nonits, the application or proposal may be recompliance with this policy or the require- turned to the institution.
(Approved by the Office of Management and Budget
ments or determinations of the IRB; and
(ii) any suspension or termination of IRB under Control Number 0990-0260.)
[56 FR 28012, 28022, June 18, 1991; 56 FR 29756, June
approval.
28, 1991, as amended at 70 FR 36328, June 23, 2005]

(c) The assurance shall be executed by an
§§46.104--46.106 [Reserved]
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.

(2)Designation of one or more IRBs established in accordance with the requirements (d) The department or agency head will
of this policy, and for which provisions are evaluate all assurances submitted in accordance with this policy through such officers
made for meeting space and sufficient
and employees of the department or agency
staff to support the IRB's review and reand such experts or consultants engaged for
cordkeeping duties.

6

45 CFR 46

§46.110 Expedited review procedures for
certain kinds of research involving no
(a) Each IRB shall have at least five memIn order to fulfill the requirements of this
more than minimal risk, and for minor
bers, with varying backgrounds to promote policy each IRB shall:
changes in approved research.
complete and adequate review of research
(a) Follow written procedures in the same
(a) The Secretary, HHS, has established, and
activities commonly conducted by the instipublished as a Notice in the FEDERAL
detail as described in §46.103(b)(4) and, to
tution. The IRB shall be sufficiently qualiREGISTER, a list of categories of research
the extent required by, §46.103(b)(5).
fied through the experience and expertise of
that may be reviewed by the IRB through an
its members, and the diversity of the mem- (b) Except when an expedited review proce- expedited review procedure. The list will be
bers, including consideration of race, gender, dure is used (see §46.110), review proposed amended, as appropriate, after consultation
with other departments and agencies,
and cultural backgrounds and sensitivity to research at convened meetings at which a
through periodic republication by the Secremajority
of
the
members
of
the
IRB
are
such issues as community attitudes, to protary, HHS, in the FEDERAL REGISTER.
present, including at least one member
mote respect for its advice and counsel in
whose primary concerns are in nonscientific A copy of the list is available from the Ofsafeguarding the rights and welfare of hufice for Human Research Protections, HHS,
man subjects. In addition to possessing the areas. In order for the research to be apor any successor office.
professional competence necessary to review proved, it shall receive the approval of a
(b) An IRB may use the expedited review
specific research activities, the IRB shall be majority of those members present at the
procedure to review either or both of the
meeting.
able to ascertain the acceptability of profollowing:
posed research in terms of institutional com- §46.109 IRB review of research.
(1) some or all of the research appearing
mitments and regulations, applicable law,
on the list and found by the reviewer(s) to
(a)
An
IRB
shall
review
and
have
authority
and standards of professional conduct and
involve no more than minimal risk,
to
approve,
require
modifications
in
(to
sepractice. The IRB shall therefore include
(2) minor changes in previously approved
persons knowledgeable in these areas. If an cure approval), or disapprove all research
research during the period (of one year or
IRB regularly reviews research that involves activities covered by this policy.
less) for which approval is authorized.
a vulnerable category of subjects, such as
(b) An IRB shall require that information
Under an expedited review procedure, the
children, prisoners, pregnant women, or
given to subjects as part of informed conhandicapped or mentally disabled persons,
sent is in accordance with §46.116. The IRB review may be carried out by the IRB chairconsideration shall be given to the inclusion may require that information, in addition to person or by one or more experienced reviewers designated by the chairperson from
of one or more individuals who are knowl- that specifically mentioned in §46.116, be
among members of the IRB. In reviewing
edgeable about and experienced in working given to the subjects when in the IRB's judg- the research, the reviewers may exercise all
with these subjects.
ment the information would meaningfully
of the authorities of the IRB except that the
add to the protection of the rights and wel- reviewers may not disapprove the research.
(b) Every nondiscriminatory effort will be
A research activity may be disapproved only
made to ensure that no IRB consists entirely fare of subjects.
after review in accordance with the nonof men or entirely of women, including the (c) An IRB shall require documentation of
expedited procedure set forth in §46.108(b).
institution's consideration of qualified perinformed consent or may waive documenta(c) Each IRB which uses an expedited resons of both sexes, so long as no selection is tion in accordance with §46.117.
view procedure shall adopt a method for
made to the IRB on the basis of gender. No
keeping all members advised of research
(d)
An
IRB
shall
notify
investigators
and
the
IRB may consist entirely of members of one
proposals which have been approved under
institution in writing of its decision to approfession.
prove or disapprove the proposed research the procedure.
(c) Each IRB shall include at least one mem- activity, or of modifications required to se- (d) The department or agency head may
ber whose primary concerns are in scientific cure IRB approval of the research activity. If restrict, suspend, terminate, or choose not to
authorize an institution's or IRB's use of the
areas and at least one member whose prithe IRB decides to disapprove a research
mary concerns are in nonscientific areas.
activity, it shall include in its written notifica- expedited review procedure.
(d) Each IRB shall include at least one mem- tion a statement of the reasons for its deci- [56 FR 28012, 28022, June 18, 1991, as amended at 70
ber who is not otherwise affiliated with the sion and give the investigator an opportunity FR 36328, June 23, 2005]
§46.111 Criteria for IRB approval of reinstitution and who is not part of the imme- to respond in person or in writing.
diate family of a person who is affiliated
(e) An IRB shall conduct continuing review search.
with the institution.
(a) In order to approve research covered by
of research covered by this policy at interthis policy the IRB shall determine that all of
vals
appropriate
to
the
degree
of
risk,
but
(e) No IRB may have a member participate
the following requirements are satisfied:
not less than once per year, and shall have
in the IRB's initial or continuing review of
(1) Risks to subjects are minimized: (i) By
any project in which the member has a con- authority to observe or have a third party
using procedures which are consistent
flicting interest, except to provide informa- observe the consent process and the research.
with sound research design and which do
tion requested by the IRB.
not unnecessarily expose subjects to risk,
(Approved by the Office of Management and Budget
(f) An IRB may, in its discretion, invite indi- under Control Number 0990-0260.)
and (ii) whenever appropriate, by using
viduals with competence in special areas to
procedures already being performed on
[56 FR 28012, 28022, June 18, 1991, as amended at 70
assist in the review of issues which require
the subjects for diagnostic or treatment
FR 36328, June 23, 2005]
expertise beyond or in addition to that availpurposes.
able on the IRB. These individuals may not
vote with the IRB
§46.107 IRB membership.

§46.108 IRB functions and operations.

45 CFR 46

7

provided to subjects, as required by
Suspension or termination of
(2) Risks to subjects are reasonable in rela- §46.113
§46.116(b)(5).
IRB approval of research.
tion to anticipated benefits, if any, to subjects, and the importance of the knowl(b) The records required by this policy shall
An IRB shall have authority to suspend or
edge that may reasonably be expected to
be retained for at least 3 years, and records
terminate approval of research that is not
result. In evaluating risks and benefits, the being conducted in accordance with the
relating to research which is conducted shall
IRB should consider only those risks and IRB's requirements or that has been associ- be retained for at least 3 years after complebenefits that may result from the research
tion of the research. All records shall be
(as distinguished from risks and benefits of ated with unexpected serious harm to subaccessible for inspection and copying by
jects. Any suspension or termination of ap- authorized representatives of the departtherapies subjects would receive even if
not participating in the research). The IRB proval shall include a statement of the reament or agency at reasonable times and in a
sons for the IRB's action and shall be reshould not consider possible long-range
reasonable manner.
effects of applying knowledge gained in
ported promptly to the investigator, appro- (Approved by the Office of Management and Budget
the research (for example, the possible
priate institutional officials, and the depart- under Control Number 0990-0260.)
effects of the research on public policy) as ment or agency head.
among those research risks that fall within
[56 FR 28012, 28022, June 18, 1991, as amended at 70
(Approved by the Office of Management and Budget
the purview of its responsibility.
FR 36328, June 23, 2005]
under Control Number 0990-0260.)
(3) Selection of subjects is equitable. In
§46.116 General requirements for in[56 FR 28012, 28022, June 18, 1991, as amended at 70
making this assessment the IRB should
formed consent.
FR 36328, June 23, 2005]
take into account the purposes of the reExcept as provided elsewhere in this policy,
§46.114 Cooperative research.
search and the setting in which the reno investigator may involve a human being
search will be conducted and should be
Cooperative research projects are those pro- as a subject in research covered by this polparticularly cognizant of the special prob- jects covered by this policy which involve
icy unless the investigator has obtained the
lems of research involving vulnerable
more than one institution. In the conduct of legally effective informed consent of the
populations, such as children, prisoners,
cooperative research projects, each institusubject or the subject's legally authorized
pregnant women, mentally disabled pertion is responsible for safeguarding the
representative. An investigator shall seek
sons, or economically or educationally
rights and welfare of human subjects and for such consent only under circumstances that
disadvantaged persons.
complying with this policy. With the approvide the prospective subject or the repre(4) Informed consent will be sought from proval of the department or agency head, an sentative sufficient opportunity to consider
institution participating in a cooperative
each prospective subject or the subject's
whether or not to participate and that minilegally authorized representative, in accor- project may enter into a joint review armize the possibility of coercion or undue
dance with, and to the extent required by rangement, rely upon the review of another influence. The information that is given to
qualified IRB, or make similar arrangements the subject or the representative shall be in
§46.116.
for avoiding duplication of effort.
language understandable to the subject or
(5) Informed consent will be appropriately
the representative. No informed consent,
§46.115 IRB records.
documented, in accordance with, and to
whether oral or written, may include any
the extent required by §46.117.
(a) An institution, or when appropriate an
exculpatory language through which the
IRB, shall prepare and maintain adequate
(6) When appropriate, the research plan
subject or the representative is made to
makes adequate provision for monitoring documentation of IRB activities, including
waive or appear to waive any of the subject's
the following:
the data collected to ensure the safety of
legal rights, or releases or appears to release
subjects.
the investigator, the sponsor, the institution
(1) Copies of all research proposals reor its agents from liability for negligence.
viewed, scientific evaluations, if any, that
(7) When appropriate, there are adequate
accompany the proposals, approved sam- (a) Basic elements of informed consent.
provisions to protect the privacy of subple consent documents, progress reports
jects and to maintain the confidentiality of
Except as provided in paragraph (c) or (d) of
submitted by investigators, and reports of this section, in seeking informed consent the
data.
injuries to subjects.
following information shall be provided to
(b) When some or all of the subjects are
each subject:
(2)
Minutes
of
IRB
meetings
which
shall
likely to be vulnerable to coercion or undue
be in sufficient detail to show attendance
influence, such as children, prisoners, preg(1) A statement that the study involves
at the meetings; actions taken by the IRB;
nant women, mentally disabled persons, or
research, an explanation of the purposes
the vote on these actions including the
economically or educationally disadvantaged
of the research and the expected duration
number of members voting for, against,
persons, additional safeguards have been
of the subject's participation, a description
and abstaining; the basis for requiring
included in the study to protect the rights
of the procedures to be followed, and
changes in or disapproving research; and a
and welfare of these subjects.
identification of any procedures which are
written summary of the discussion of conexperimental;
§46.112 Review by institution.
troverted issues and their resolution.
(2) A description of any reasonably foreResearch covered by this policy that has
(3) Records of continuing review activities. seeable risks or discomforts to the subject;
been approved by an IRB may be subject to
(4) Copies of all correspondence between
(3) A description of any benefits to the
further appropriate review and approval or
the IRB and the investigators.
subject or to others which may reasonably
disapproval by officials of the institution.
be expected from the research;
However, those officials may not approve
(5) A list of IRB members in the same
the research if it has not been approved by
detail as described in §46.103(b)(3).
(4) A disclosure of appropriate alternative
an IRB.
procedures or courses of treatment, if any,
(6) Written procedures for the IRB in the
that might be advantageous to the subject;
same detail as described in §46.103(b)(4)
and §46.103(b)(5).
(5) A statement describing the extent, if
any, to which confidentiality of records
(7) Statements of significant new findings
identifying the subject will be maintained;

8

45 CFR 46

(6) For research involving more than mini- (2) The research could not practicably be approve a written summary of what is to be
mal risk, an explanation as to whether any
carried out without the waiver or alterasaid to the subject or the representative.
compensation and an explanation as to
tion.
Only the short form itself is to be signed by
whether any medical treatments are avail- (d) An IRB may approve a consent procethe subject or the representative. However,
able if injury occurs and, if so, what they
the witness shall sign both the short form
dure which does not include, or which alters, and a copy of the summary, and the person
consist of, or where further information
some or all of the elements of informed
may be obtained;
actually obtaining consent shall sign a copy
consent set forth in this section, or waive
of the summary. A copy of the summary
(7) An explanation of whom to contact for the requirements to obtain informed conanswers to pertinent questions about the
sent provided the IRB finds and documents shall be given to the subject or the representative, in addition to a copy of the short
research and research subjects' rights, and that:
form.
whom to contact in the event of a re1)
The
research
involves
no
more
than
minisearch-related injury to the subject; and
(c) An IRB may waive the requirement for
mal risk to the subjects;
the investigator to obtain a signed consent
(8) A statement that participation is volun(2) The waiver or alteration will not adform for some or all subjects if it finds eitary, refusal to participate will involve no
versely affect the rights and welfare of the
ther:
penalty or loss of benefits to which the
subject is otherwise entitled, and the sub- subjects;
(1) That the only record linking the subject
ject may discontinue participation at any
(3) The research could not practicably be
and the research would be the consent docutime without penalty or loss of benefits to carried out without the waiver or alteration; ment and the principal risk would be potenwhich the subject is otherwise entitled.
and
tial harm resulting from a breach of confi(b) Additional elements of informed con(4) Whenever appropriate, the subjects will dentiality. Each subject will be asked
the subject wants documentation
sent. When appropriate, one or more of the be provided with additional pertinent infor- whether
linking the subject with the research, and the
following elements of information shall also mation after participation.
subject's wishes will govern; or
be provided to each subject:
(e) The informed consent requirements in
(1) A statement that the particular treatthis policy are not intended to preempt any (2) That the research presents no more than
risk of harm to subjects and inment or procedure may involve risks to
applicable federal, state, or local laws which minimal
volves no procedures for which written conthe subject (or to the embryo or fetus, if
require additional information to be dissent is normally required outside of the rethe subject is or may become pregnant)
closed in order for informed consent to be
search context.
which are currently unforeseeable;
legally effective.
cases in which the documentation re(2) Anticipated circumstances under which (f) Nothing in this policy is intended to limit In
quirement is waived, the IRB may require
the subject's participation may be termithe authority of a physician to provide emernated by the investigator without regard to gency medical care, to the extent the physi- the investigator to provide subjects with a
written statement regarding the research.
the subject's consent;
cian is permitted to do so under applicable
(Approved by the Office of Management and Budget
(3) Any additional costs to the subject that federal, state, or local law.
under Control Number 0990-0260.)
may result from participation in the re(Approved by the Office of Management and Budget
search;
under Control Number 0990-0260.)
[56 FR 28012, 28022, June 18, 1991, as amended at 70
(4) The consequences of a subject's deci- [56 FR 28012, 28022, June 18, 1991, as amended at 70 FR 36328, June 23, 2005]
sion to withdraw from the research and
§46.118 Applications and proposals lackFR 36328, June 23, 2005]
procedures for orderly termination of par- §46.117 Documentation of informed coning definite plans for involvement of
ticipation by the subject;
human subjects.
sent.
(5) A statement that significant new findCertain types of applications for grants, co(a) Except as provided in paragraph (c) of
ings developed during the course of the
this section, informed consent shall be docu- operative agreements, or contracts are subresearch which may relate to the subject's mented by the use of a written consent form mitted to departments or agencies with the
willingness to continue participation will
knowledge that subjects may be involved
approved by the IRB and signed by the sub- within the period of support, but definite
be provided to the subject; and
ject or the subject's legally authorized repreplans would not normally be set forth in the
(6) The approximate number of subjects
sentative. A copy shall be given to the perapplication or proposal. These include acinvolved in the study.
son signing the form.
tivities such as institutional type grants when
(c) An IRB may approve a consent proceselection of specific projects is the institu(b) Except as provided in paragraph (c) of
dure which does not include, or which alters, this section, the consent form may be either tion's responsibility; research training grants
some or all of the elements of informed
in which the activities involving subjects
of the following:
consent set forth above, or waive the reremain to be selected; and projects in which
quirement to obtain informed consent pro- (1) A written consent document that emhuman subjects' involvement will depend
bodies the elements of informed consent
vided the IRB finds and documents that:
required by §46.116. This form may be read upon completion of instruments, prior anistudies, or purification of compounds.
(1) The research or demonstration project to the subject or the subject's legally author- mal
These applications need not be reviewed by
is to be conducted by or subject to the
ized representative, but in any event, the
an IRB before an award may be made. Howapproval of state or local government offi- investigator shall give either the subject or
ever, except for research exempted or
cials and is designed to study, evaluate, or the representative adequate opportunity to
waived under §46.101(b) or (i), no human
otherwise examine: (i) public benefit or
read it before it is signed; or
subjects may be involved in any project supservice programs; (ii) procedures for obported by these awards until the project has
(2)
A
short
form
written
consent
document
taining benefits or services under those
been reviewed and approved by the IRB, as
stating that the elements of informed conprograms; (iii) possible changes in or alter- sent required by §46.116 have been preprovided in this policy, and certification
natives to those programs or procedures;
submitted, by the institution, to the departsented
orally
to
the
subject
or
the
subject's
or (iv) possible changes in methods or
legally authorized representative. When this ment or agency.
levels of payment for benefits or services method is used, there shall be a witness to
under those programs; and
the oral presentation. Also, the IRB shall

45 CFR 46
§46.119 Research undertaken without the
directed the scientific and technical aspects
intention of involving human subof an activity has/have, in the judgment of
jects.
the department or agency head, materially
In the event research is undertaken without failed to discharge responsibility for the prothe intention of involving human subjects,
tection of the rights and welfare of human
but it is later proposed to involve human
subjects (whether or not the research was
subjects in the research, the research shall
subject to federal regulation).
first be reviewed and approved by an IRB,
§46.124 Conditions.
as provided in this policy, a certification
submitted, by the institution, to the depart- With respect to any research project or any
ment or agency, and final approval given to class of research projects the department or
the proposed change by the department or
agency head may impose additional condiagency.
tions prior to or at the time of approval
when in the judgment of the department or
§46.120 Evaluation and disposition of
agency head additional conditions are necesapplications and proposals for research to be conducted or supported sary for the protection of human subjects.
by a Federal Department or Agency.
(a) The department or agency head will
Subpart B
evaluate all applications and proposals inAdditional Protections for Pregvolving human subjects submitted to the
nant Women, Human Fetuses
department or agency through such officers and Neonates Involved in Reand employees of the department or agency
and such experts and consultants as the de- search
partment or agency head determines to be
Source: 66 FR 56778, Nov. 13, 2001, unless otherwise
appropriate. This evaluation will take into
noted.
consideration the risks to the subjects, the
§46.201 To what do these regulations
adequacy of protection against these risks,
apply?
the potential benefits of the research to the
subjects and others, and the importance of
(a) Except as provided in paragraph (b) of
the knowledge gained or to be gained.
this section, this subpart applies to all research involving pregnant women, human
(b) On the basis of this evaluation, the defetuses, neonates of uncertain viability, or
partment or agency head may approve or
disapprove the application or proposal, or
nonviable neonates conducted or supported
enter into negotiations to develop an apby the Department of Health and Human
provable one.
Services (DHHS). This includes all research
conducted in DHHS facilities by any person
§46.121 [Reserved]
and all research conducted in any facility by
§46.122 Use of Federal funds.
DHHS employees.
Federal funds administered by a department
or agency may not be expended for research (b) The exemptions at §46.101(b)(1) through
involving human subjects unless the require- (6) are applicable to this subpart.
ments of this policy have been satisfied.
(c) The provisions of §46.101(c) through (i)
§46.123 Early termination of research supare applicable to this subpart. Reference to
port: Evaluation of applications and propos- State or local laws in this subpart and in
als.
§46.101(f) is intended to include the laws of
(a) The department or agency head may
federally recognized American Indian and
require that department or agency support
Alaska Native Tribal Governments.
for any project be terminated or suspended
in the manner prescribed in applicable pro- (d) The requirements of this subpart are in
gram requirements, when the department or addition to those imposed under the other
agency head finds an institution has materi- subparts of this part.
ally failed to comply with the terms of this
§46.202 Definitions.
policy.
(b) In making decisions about supporting or The definitions in §46.102 shall be applicaapproving applications or proposals covered ble to this subpart as well. In addition, as
by this policy the department or agency head used in this subpart:
may take into account, in addition to all
(a) Dead fetus means a fetus that exhibits
other eligibility requirements and program
neither heartbeat, spontaneous respiratory
criteria, factors such as whether the appliactivity, spontaneous movement of voluncant has been subject to a termination or
suspension under paragraph (a) of this sec- tary muscles, nor pulsation of the umbilical
tion and whether the applicant or the person cord.
or persons who would direct or has/have

9
(b) Delivery means complete separation of
the fetus from the woman by expulsion or
extraction or any other means.
(c) Fetus means the product of conception
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 presumptive signs of pregnancy, such as missed menses, 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 therapy) to the point of independently maintaining heartbeat and respiration. The Secretary
may from time to time, taking into account
medical advances, publish in the FEDERAL
REGISTER guidelines to assist in determining whether a neonate is viable for purposes
of this subpart. If a neonate is viable then it
may be included in research only to the extent permitted and in accordance with the
requirements of 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 review 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, preclinical studies, including studies on pregnant
animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;

10
(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 research is the development of important biomedical knowledge which cannot be obtained by any other means;
(c) Any risk is the least possible for achieving the objectives of the research;

45 CFR 46
(1) Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.

(4) The purpose of the research is the development of important biomedical
knowledge that cannot be obtained by
other means; and

(2) Each individual providing consent under paragraph (b)(2) or (c)(5) of this section is fully informed regarding the reasonably foreseeable impact of the research
on the neonate.

(5) The legally effective informed consent
of both parents of the neonate is obtained
in accord with subpart A of this part, except that the waiver and alteration provisions of §46.116(c) and (d) do not apply.
However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements of this paragraph (c)(5), except
that the consent of the father need not be
obtained if the pregnancy resulted from
rape or incest. The consent of a legally
authorized representative of either or both
of the parents of a nonviable neonate will
not suffice to meet the requirements of
this paragraph (c)(5).

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

(d) If the research holds out the prospect of
direct benefit to the pregnant woman, the
(4) The requirements of paragraph (b) or
prospect of a direct benefit both to the preg(c) of this section have been met as applinant woman and the fetus, or no prospect of
cable.
benefit for the woman nor the fetus when
risk to the fetus is not greater than minimal (b) Neonates of uncertain viability. Until it
and the purpose of the research is the devel- has been ascertained whether or not a neoopment of important biomedical knowledge nate is viable, a neonate may not be involved
that cannot be obtained by any other means, in research covered by this subpart unless
the following additional conditions have
her consent is obtained in accord with the
been met:
informed consent provisions of subpart A
of this part;
(d) Viable neonates. A neonate, after deliv(1) The IRB determines that:
ery, that has been determined to be viable
(e) If the research holds out the prospect of
(i) The research holds out the prospect of may be included in research only to the exdirect benefit solely to the fetus then the
enhancing the probability of survival of
tent permitted by and in accord with the
consent of the pregnant woman and the
the neonate to the point of viability, and
requirements of subparts A and D of this
father is obtained in accord with the inany risk is the least possible for achieving part.
formed consent provisions of subpart A of
that objective, or
this part, except that the father's consent
§46.206 Research involving, after deliv(ii) The purpose of the research is the deneed not be obtained if he is unable to conery, the placenta, the dead fetus or
sent because of unavailability, incompetence, velopment of important biomedical
fetal material.
knowledge which cannot be obtained by
or temporary incapacity or the pregnancy
(a) Research involving, after delivery, the
other means and there will be no added
resulted from rape or incest.
placenta; the dead fetus; macerated fetal
risk to the neonate resulting from the re(f) Each individual providing consent under
material; or cells, tissue, or organs excised
search; and
paragraph (d) or (e) of this section is fully
from a dead fetus, shall be conducted only
(2) The legally effective informed consent in accord with any applicable federal, state,
informed regarding the reasonably foreseeof either parent of the neonate or, if neiable impact of the research on the fetus or
or local laws and regulations regarding such
ther parent is able to consent because of
neonate;
activities.
unavailability, incompetence, or temporary
(g) For children as defined in §46.402(a)
(b) If information associated with material
incapacity, the legally effective informed
who are pregnant, assent and permission are
described in paragraph (a) of this section is
consent of either parent's legally authorobtained in accord with the provisions of
recorded for research purposes in a manner
ized representative is obtained in accord
subpart D of this part;
with subpart A of this part, except that the that living individuals can be identified, diconsent of the father or his legally author- rectly or through identifiers linked to those
(h) No inducements, monetary or otherwise,
ized representative need not be obtained if individuals, those individuals are research
will be offered to terminate a pregnancy;
the pregnancy resulted from rape or incest. subjects and all pertinent subparts of this
(i) Individuals engaged in the research will
part are applicable.
have no part in any decisions as to the tim- (c) Nonviable neonates. After delivery non§46.207 Research not otherwise approvviable neonate may not be involved in reing, method, or procedures used to termiable which presents an opportunity
search covered by this subpart unless all of
nate a pregnancy; and
to understand, prevent, or alleviate a
the following additional conditions are met:
(j) Individuals engaged in the research will
serious problem affecting the health
(1) Vital functions of the neonate will not
have no part in determining the viability of a
or welfare of pregnant women, febe artificially maintained;
neonate.
tuses, or neonates.
(2) The research will not terminate the
§46.205 Research involving neonates.
The Secretary will conduct or fund research
heartbeat or respiration of the neonate;
that the IRB does not believe meets the
(a) Neonates of uncertain viability and nonrequirements of §46.204 or §46.205 only if:
(3)
There
will
be
no
added
risk
to
the
neoviable neonates may be involved in research
nate
resulting
from
the
research;
if all of the following conditions are met:
(a) The IRB finds that the research presents

45 CFR 46
a reasonable opportunity to further the understanding, prevention, or alleviation of a
serious problem affecting the health or welfare of pregnant women, fetuses or neonates; and

11
could affect their ability to make a truly voluntary and uncoerced decision whether or
not to participate as subjects in research, it is
the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in activities to which this
subpart is applicable.

(b) The Secretary, after consultation with a
panel of experts in pertinent disciplines (for
example: science, medicine, ethics, law) and §46.303 Definitions.
following opportunity for public review and
As used in this subpart:
comment, including a public meeting announced in the FEDERAL REGISTER, has (a) Secretary means the Secretary of Health
and Human Services and any other officer
determined either:
or employee of the Department of Health
(1) That the research in fact satisfies the
and Human Services to whom authority has
conditions of §46.204, as applicable; or
been delegated.
(2) The following:
(b) DHHS means the Department of Health
(i) The research presents a reasonable op- and Human Services.
portunity to further the understanding,
(c) Prisoner means any individual involuntarprevention, or alleviation of a serious
ily confined or detained in a penal instituproblem affecting the health or welfare of
tion. The term is intended to encompass
pregnant women, fetuses or neonates;
individuals sentenced to such an institution
(ii) The research will be conducted in acunder a criminal or civil statute, individuals
cord with sound ethical principles; and
detained in other facilities by virtue of stat(iii) Informed consent will be obtained in utes or commitment procedures which provide alternatives to criminal prosecution or
accord with the informed consent proviincarceration in a penal institution, and indisions of subpart A and other applicable
viduals detained pending arraignment, trial,
subparts of this part.
or sentencing.

Subpart C
Additional Protections Pertaining
to Biomedical and Behavioral Research Involving Prisoners as
Subjects
Source: 43 FR 53655, Nov. 16, 1978, unless otherwise
noted.

§46.301 Applicability.
(a) The regulations in this subpart are applicable to all biomedical and behavioral research conducted or supported by the Department of Health and Human Services
involving prisoners as subjects.
(b) Nothing in this subpart shall be construed 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.
(c) The requirements of this subpart are in
addition to those imposed under the other
subparts of this part.
§46.302 Purpose.
Inasmuch as prisoners may be under constraints because of their incarceration which

(d) Minimal risk is the probability and magnitude of physical or psychological harm that
is normally encountered in the daily lives, or
in the routine medical, dental, or psychological 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 Institutional Review Boards where prisoners are involved.
(a) In addition to all other responsibilities
prescribed for Institutional Review Boards
under this part, the Board shall review research 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 permissible under §46.306(a)(2);
(2) Any possible advantages accruing to
the prisoner through his or her participation 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 characteristics needed for that particular research project;
(5) The information is presented in language which is understandable to the subject population;
(6) Adequate assurance exists that parole
boards will not take into account a prisoner's participation in the research in making 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 participation, 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.
(c) The institution shall certify to the Secre-

12

45 CFR 46

tary, in such form and manner as the Secre- (b) Except as provided in paragraph (a) of
tary may require, that the duties of the
this section, biomedical or behavioral reBoard under this section have been fulfilled. search conducted or supported by DHHS
shall not involve prisoners as subjects.
§46.306 Permitted research involving
prisoners.
(a) Biomedical or behavioral research conducted or supported by DHHS may involve
prisoners as subjects only if:

Subpart D
Additional Protections for Chil(1) The institution responsible for the con- dren Involved as Subjects in Research
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 following:
(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 subjects;
(ii) Study of prisons as institutional structures or of prisoners as incarcerated persons, 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 hepatitis which is much more prevalent in prisons than elsewhere; and research on social
and psychological problems such as alcoholism, drug addiction, and sexual assaults) provided that the study may proceed only after the Secretary has consulted
with appropriate experts including experts
in penology, medicine, and ethics, and
published notice, in the FEDERAL REGISTER, of his intent to approve such research; or

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

§46.401 To what do these regulations
apply?

ments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.
(b) Assent means a child's affirmative agreement to participate in research. Mere failure
to object should not, absent affirmative
agreement, be construed as assent.
(c) Permission means the agreement of parent
(s) or guardian to the participation of their
child or ward in research.
(d) Parent means a child's biological or adoptive parent.
(e) Guardian means an individual who is authorized under applicable State or local law
to consent on behalf of a child to general
medical care.

(a) This subpart applies to all research involving children as subjects, conducted or
supported by the Department of Health and
§46.403 IRB duties.
Human Services.
(1) This includes research conducted by
Department employees, except that each
head of an Operating Division of the Department may adopt such nonsubstantive,
procedural modifications as may be appropriate from an administrative standpoint.

In addition to other responsibilities assigned
to IRBs under this part, each IRB shall review research covered by this subpart and
approve only research which satisfies the
conditions of all applicable sections of this
subpart.

(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 applicability of some or all of the requirements of
these regulations for research of this type.

§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.

(b) Exemptions at §46.101(b)(1) and (b)(3)
through (b)(6) are applicable to this subpart. §46.405 Research involving greater than
The exemption at §46.101(b)(2) regarding
minimal risk but presenting the
educational tests is also applicable to this
prospect of direct benefit to the indisubpart. However, the exemption at §46.101
vidual subjects.
(b)(2) for research involving survey or interHHS will conduct or fund research in which
view procedures or observations of public
behavior does not apply to research covered the IRB finds that more than minimal risk to
by this subpart, except for research involv- children is presented by an intervention or
(iv) Research on practices, both innovative ing observation of public behavior when the procedure that holds out the prospect of
direct benefit for the individual subject, or
and accepted, which have the intent and
investigator(s) do not participate in the acby a monitoring procedure that is likely to
reasonable probability of improving the
tivities being observed.
contribute to the subject's well-being, only if
health or well-being of the subject. In
(c) The exceptions, additions, and provisions the IRB finds that:
cases in which those studies require the
for waiver as they appear in paragraphs (c)
assignment of prisoners in a manner conthrough (i) of §46.101 of subpart A are ap- (a) The risk is justified by the anticipated
sistent with protocols approved by the
benefit to the subjects;
plicable to this subpart.
IRB to control groups which may not
[48 FR 9818, Mar.8, 1983; 56 FR 28032, June 18, 1991; (b) The relation of the anticipated benefit to
benefit from the research, the study may
the risk is at least as favorable to the subjects
proceed only after the Secretary has con- 56 FR 29757, June 28, 1991.]
as that presented by available alternative
sulted with appropriate experts, including §46.402 Definitions.
experts in penology, medicine, and ethics, The definitions in §46.102 of subpart A shall approaches; and
and published notice, in the FEDERAL
be applicable to this subpart as well. In addi- (c) Adequate provisions are made for solicitREGISTER, of the intent to approve such tion, as used in this subpart:
ing the assent of the children and permission
research.
of their parents or guardians, as set forth in
(a) Children are persons who have not at§46.408.
tained the legal age for consent to treat-

45 CFR 46

13

§46.406 Research involving greater than (i) the research presents a reasonable oppor- reasonably available, or when only one parminimal risk and no prospect of di- tunity to further the understanding, preven- ent has legal responsibility for the care and
rect benefit to individual subjects,
tion, or alleviation of a serious problem af- custody of the child.
but likely to yield generalizable
fecting the health or welfare of children;
(c) In addition to the provisions for waiver
knowledge about the subject's disor(ii) the research will be conducted in accor- contained in §46.116 of subpart A, if the
der or condition.
IRB determines that a research protocol is
dance with sound ethical principles;
HHS will conduct or fund research in which
designed for conditions or for a subject
(iii) adequate provisions are made for solicitthe IRB finds that more than minimal risk to
population for which parental or guardian
ing the assent of children and the permission
children is presented by an intervention or
permission is not a reasonable requirement
of their parents or guardians, as set forth in
procedure that does not hold out the prosto protect the subjects (for example, ne§46.408.
pect of direct benefit for the individual subglected or abused children), it may waive the
ject, or by a monitoring procedure which is §46.408 Requirements for permission by consent requirements in Subpart A of this
parents or guardians and for assent part and paragraph (b) of this section, pronot likely to contribute to the well-being of
by children.
the subject, only if the IRB finds that:
vided an appropriate mechanism for protecting the children who will participate as
(a) The risk represents a minor increase over (a) In addition to the determinations resubjects in the research is substituted, and
quired
under
other
applicable
sections
of
minimal risk;
provided further that the waiver is not inthis subpart, the IRB shall determine that
(b) The intervention or procedure presents
adequate provisions are made for soliciting consistent with federal, state, or local law.
experiences to subjects that are reasonably
the assent of the children, when in the judg- The choice of an appropriate mechanism
commensurate with those inherent in their
ment of the IRB the children are capable of would depend upon the nature and purpose
actual or expected medical, dental, psychoof the activities described in the protocol,
providing assent. In determining whether
logical, social, or educational situations;
the risk and anticipated benefit to the rechildren are capable of assenting, the IRB
search subjects, and their age, maturity,
(c) The intervention or procedure is likely to shall take into account the ages, maturity,
status, and condition.
yield generalizable knowledge about the
and psychological state of the children insubjects' disorder or condition which is of
volved. This judgment may be made for all (d) Permission by parents or guardians shall
vital importance for the understanding or
children to be involved in research under a be documented in accordance with and to
amelioration of the subjects' disorder or
particular protocol, or for each child, as the the extent required by §46.117 of subpart A.
condition; and
IRB deems appropriate. If the IRB deter(e) When the IRB determines that assent is
(d) Adequate provisions are made for solicit- mines that the capability of some or all of
required, it shall also determine whether and
ing assent of the children and permission of the children is so limited that they cannot
how assent must be documented.
reasonably be consulted or that the interventheir parents or guardians, as set forth in
§46.409 Wards.
tion or procedure involved in the research
§46.408.
holds out a prospect of direct benefit that is (a) Children who are wards of the state or
§46.407 Research not otherwise approv- important to the health or well-being of the
able which presents an opportunity children and is available only in the context any other agency, institution, or entity can
to understand, prevent, or alleviate a of the research, the assent of the children is be included in research approved under
§46.406 or §46.407 only if such research is:
serious problem affecting the health not a necessary condition for proceeding
or welfare of children.
(1) Related to their status as wards; or
with the research. Even where the IRB determines
that
the
subjects
are
capable
of
HHS will conduct or fund research that the
(2) Conducted in schools, camps, hospiassenting, the IRB may still waive the assent
IRB does not believe meets the requiretals, institutions, or similar settings in
ments of §46.404, §46.405, or §46.406 only requirement under circumstances in which
which the majority of children involved as
consent may be waived in accord with
if:
subjects are not wards.
§46.116 of Subpart A.
(a) the IRB finds that the research presents a
(b) If the research is approved under parareasonable opportunity to further the under- (b) In addition to the determinations regraph (a) of this section, the IRB shall restanding, prevention, or alleviation of a seri- quired under other applicable sections of
quire appointment of an advocate for each
ous problem affecting the health or welfare this subpart, the IRB shall determine, in
child who is a ward, in addition to any other
accordance with and to the extent that con- individual acting on behalf of the child as
of children; and
sent is required by §46.116 of Subpart A,
guardian or in loco parentis. One individual
(b) the Secretary, after consultation with a
that adequate provisions are made for solic- may serve as advocate for more than one
panel of experts in pertinent disciplines (for iting the permission of each child's parents
example: science, medicine, education, eth- or guardian. Where parental permission is to child. The advocate shall be an individual
ics, law) and following opportunity for pub- be obtained, the IRB may find that the per- who has the background and experience to
act in, and agrees to act in, the best interests
lic review and comment, has determined
mission of one parent is sufficient for reof the child for the duration of the child's
either:
search to be conducted under §46.404 or
participation in the research and who is not
(1) that the research in fact satisfies the con- §46.405. Where research is covered by
associated in any way (except in the role as
§§46.406 and 46.407 and permission is to be advocate or member of the IRB) with the
ditions of §46.404, §46.405, or §46.406, as
obtained from parents, both parents must
applicable, or (2) the following:
research, the investigator(s), or the guardian
give their permission unless one parent is
organization.
deceased, unknown, incompetent, or not

14

Subpart E
Registration of Institutional Review Boards
Source: 74 FR 2399, January 15, 2009, unless otherwise
noted.

45 CFR 46
(f) The approximate number of full-time
equivalent positions devoted to the IRB's
administrative activities.
§46.503 When must an IRB be registered?

An IRB must be registered before it can be
designated under an assurance approved for
Each IRB that is designated by an institution federalwide use by OHRP under §46.103(a).
under an assurance of compliance approved IRB registration becomes effective when
for federalwide use by the Office for Human reviewed and accepted by OHRP.
Research Protections (OHRP) under
§46.103(a) and that reviews research involv- The registration will be effective for 3 years.
ing human subjects conducted or supported §46.504 How must an IRB be regisby the Department of Health and Human
tered?
Services (HHS) must be registered with
Each IRB must be registered electronically
HHS. An individual authorized to act on
behalf of the institution or organization op- through http://ohrp.cit.nih.gov/efile unless
erating the IRB must submit the registration an institution or organization lacks the ability to register its IRB(s) electronically. If an
information.
institution or organization lacks the ability to
§46.502 What information must be pro- register an IRB electronically, it must send
vided when registering an IRB?
its IRB registration information in writing to
OHRP.
The following information must be provided to HHS when registering an IRB:
§46.505 When must IRB registration
information be renewed or updated?
(a) The name, mailing address, and street
address (if different from the mailing ad(a) Each IRB must renew its registration
dress) of the institution or organization op- every 3 years.
erating the IRB(s); and the name, mailing
(b) The registration information for an IRB
address, phone number, facsimile number,
must be updated within 90 days after
and electronic mail address of the senior
officer or head official of that institution or changes occur regarding the contact person
organization who is responsible for oversee- who provided the IRB registration information or the IRB chairperson. The updated
ing activities performed by the IRB.
registration information must be submitted
(b) The name, mailing address, phone num- in accordance with §46.504.
ber, facsimile number, and electronic mail
address of the contact person providing the (c) Any renewal or update that is submitted
to, and accepted by, OHRP begins a new 3registration information.
year effective period.
(c) The name, if any, assigned to the IRB by
the institution or organization, and the IRB's (d) An institution's or organization's decision to disband a registered IRB which it is
mailing address, street address (if different
operating also must be reported to OHRP in
from the mailing address), phone number,
writing within 30 days after permanent cesfacsimile number, and electronic mail adsation of the IRB's review of HHSdress.
conducted or -supported research.
(d) The name, phone number, and electronic
mail address of the IRB chairperson.
§46.501 What IRBs must be registered?

(e)(1) The approximate numbers of:
(i) All active protocols; and
(ii) Active protocols conducted or supported 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.