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45 CFR 46
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Page 4
FART 4&— PKv'T
(
: f"
HUMAN
SUBJECTS
jbubparl A— Basic HHS Poiicy for
Protectionj>f Human Research
Subjects
See.
101
To whit do these regulations apply?
46.102
Definitions.
46.103
Assurances
1 04
Section reserved
46.105
Section reserved,
46 106
Section reserved,
107
IRB membership.
46. 108
IRB functions and operations.
109
IRB review of research.
46.
1 10
Expedited review procedures for
certain kinds of research involving no
more than minimal risk, and for minor
changes in approved research.
46 M
Criteria for IRB approval of
research.
112
Review by institution.
46.
1 13
Suspension or termination of IRB
approval of research.
46.
1 14
Cooperative research.
46.115
IRB records
116
General requirements for informed
consent.
46.
1 17
Documentation of informed
consent.
46.118
Applications and proposals lacking
definite plans for involvement of human
subjects.
1 9
Research undertaken without the
intention of involving human subjects.
46.120
Evaluation and disposition of
applications and proposals.
46. !21
Investigational new drug or device
30-day delay requirement.
46.122
Use of federal funds.
46.123
Early termination of research
funding; evaluation of subsequent
applications and proposals.
1 24
Conditions.
Subpart B—Additional Protections
Pertaining to Research
Development* and Related
Activities Involving Fetuses,
Pregnant Women, and Human
In Vitro Fertilization
Sec.
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
*. .
•
•;
:<
x
:f
v
r
i.irsri,-
*
r
.
.
won-en. w human in vuio Uculujtuir.
46.201
General hmilaluKis.
4o.2Cm
Auivijio directed tnuard
p:rgr.«,r,t
women as subjects.
wo.uuis
Activities directed toward fetuses m
utero at subjects.
46.209
Activities directed toward fetuses ex
titerw. including nor.viahie Ictuses.
subjects.
46.210
Activities involving the dead
fetus,
feta! material, or the placenta.
46.21
Modification or waiver of specific
requirements.
Subpart C— Additional Protections
Pertaining to Biomedical and
Behavioral Research Involving
Prisoners as Subjects
Sec
46.301
Applicability.
46.302
Purpose.
46.303
Definitions.
46.304
Composition of Institutional Review
Boards where prisoners arc involved.
46.305
Additional duties of the Institutional
Review Boards where prisoners arc
involved.
„
46.306
Permuted activities involving
prisoners.
Subpart D—Additional Protections
for Children Involved as Subjects in
Research
See.
46.401
To what do these regulations apply?
46.402
Definittons.
46.403
IRB duties.
46.404
Research not involving greater than
minimal
risk,
46.405
Research involving greater than
minimal risk but presenting the prospect
of direct benefit to the individual subjects.
46.406
Research involving greater than
minimal riak and no prospect of direct
benefit to individual subjects, but likely to
yield gcneralizablc 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, sec. 474(a), 88
Star 352 (42 I’.S.C. 2B9/-3u».
' i-^pArt A — Lassie HHS Folic)
for
Protection of Human Research
Sirftirct*
S'M.nre
46 FR 8386, ianuary 26,
1981, 48 FR
9269, March 4,
1983.
fi 46.101
To what do these
regulations apply?
(a) Except as provided in
paragraph (b) of this section, this
subpart applies to
all research
involving human subjects conducted
by ihc Department of Health and
Human Services or funded in whole
or in part by a Department grant,
contract, cooperative agreement or
fellowship.
(1) This includes research
conducted by Department employees,
except each Principal Operating
Component head may adopt such
nonsubstantive, procedural
modifications as may be appropriate
from
art administrative standpoint.
(2)
It also includes research
conducted or funded by the
Department of Health and Human
Services outside the United States,
but in appropriate circumstances, the
Secretary may, under paragraph (e) of
this section waive the applicability of
some or all of the requirements of
these regulations for research of this
type.
(b) Research activities in which the
only involvement of human subjects
will be in one or more of the
following^atcgorics are exempt from
these regulations unless the research
is covered by other subparts of this
part;
(1) Research conducted
in
established or commonly accepted
educational settings, involving
norma! 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),
if
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iiSlS
45 CFR 44
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Pape 5
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’
'.-riufi-'-n take;
tram
ihv*
m^-u-
is uvorded in such
a manner that
f \
subjects cannot be identified, direct!)
^
nr -through identifiers linked
to
iIa
subjects.
(3)
Research involving survey or
interview procedures, except where
alf of the following conditions exist:
(i) responses are recorded
in such a
manner that the human subjects can
be identified, directly or through
identifiers linked to the subjects,
(it)
the subject’s responses,
if they
be-.ame known outside the research,
could reasonably place the subject
at
risk of criminal or civil
liability or be
damaging to the subject's financial
standing or employability, and
(iii)
the research deals with sensitive
aspects of the subject's own behavior,
such as illegal conduct, drug use,
sexual behavior, or use of alcohol.
All research involving survey or
interview procedures
is exempt,
without exception, when the
respondents are elected or appointed
public officials or candidates for
public office.
(4)
Research involving the
observation (including observation by
participants) of public behavior,
except where
ail of the following
conditions exist:
(i) observations are
recorded
in such
a manner that the
human subjects can be identified,
directly or through identifiers linked
to the subjects,
(ii) the observations
recorded about the individual,
if they
became known outside the research,
could reasonably place the subject
at
risk of criminal or civil
liability or be
damaging to the subject’s financial
standing or employability, and
(iii)
the research deals with sensitive
aspects of the subject's own behavior
such as illegal conduct, drug use.
sexual behavior, or use of alcohol.
(5)
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
i V ^
t
‘
_ a," Ti n be
i e
.
I ii
i
.
or through
identifiers linked
to the
'
suajects.
(6) Unless specifically required by
statute
(ruiCi crtCepi to the extent
specified
in paragraph (i)) f research
and demonstration projects which
ar<3 conducted by or subject to
tf.r
approval of the Department of
Health and Human Services, and
which are designed to study,
evaluate, or otherwise examine:
(i)
programs under the Social Security
Act, or other 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; or (iv) possible
changes in methods or levels of
payment tor benefits or services
under those programs.
(c) The Secretary has
final
authority to determine whether a
particular activity
is covered by these
regulations.
(d) The Secretary may require that
specific research activities or classes
of research activities conducted or
funded by the Department, but not
otherwise covered by these
regulations, comply with some or all
of these regulations.
(e) The Secretary may also waive
applicability of these regulations to
specific research activities or classes
of research activities, otherwise
covered by these regulations. Notices
of these actions will be published in
the Federal Register as they occur.
(0 No individual may receive
Department funding for research
covered by these regulations unless
the individual
is affiliated with or
sponsored by an institution which
assumes responsibility for the
research under an assurance laiisfving
the requirements of this part, or the
individual makes other arrangements
with the Department.
(g) Compliance with these
regulations
will
in no way render
inapplicable pertinent federal, nuu.\
or local laws or regulations.
b
- uaoafi of
these
rer
at ions contains a separate
sre ^-'.n iVs. nbrng to whjt? the subpan
jppbes. Research which
is covered
by more than one .subpart shall
comply w
t tii
ail applicable subparts,
(i)
If, following review of
.**( 1
- -if
: a-
activities mat
. arc
exempt from these regulations under
paragraph (bX6), the Secretary
determines that a research or
demonstration project presents a
danger to the physical, mental, or
emotional w ell-being of a participant
or subject of the research or
demonstration project, then federal
funds may not be expended for such
a project without the written,
informed consent of each participant
or subject.
§ 46.102
Definitions.
(a) “Secretary" means the
Secretary of Health and Human
Services and any other officer or
employee of the Department of
Health and Human Services to whom
authority has been delegated.
(b) "Department" or "HHS"
means the Department of Health and
Human Services.
(d)
•‘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.
(e) “Research” incans a
systematic investigation designed to
develop or contribute to gcneralizable
knowledge.
Activities which meet
this definition constitute “research
for purposes of these regulations,
whether or not they are supported or
funded under a program which
is
considered research for other
purposes. For example, some
“demonstration" and “service”
programs may include research
activities.
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45 CFR 46
(0 “Hum*? subject
1 * means
a
individual about wh^m an
5 4ii.i ( ?
A^ usances.
(a)
l~.airH in
'fur ion enpare*
unpaid consultant
in IKR
f tK m 1 *c r 'd'ti p
sit i’i
i hr
ro
r he
iw..»uier p^it ssioiwi
ut
student) conducting research obtains
[
!
) data through
iiiter ver ti«>n or
interaction with the individual,
or (2)
idem
i liable private information,
‘intervention V includes both
physical procedures by which data are
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-k mt> h*
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.
i. ^
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1 ' ' *
«-
i
' in* j'uuv out
f
arid manipulations of the subject or
the subject’s environment that arc
performed for research purposes.
‘interactionT
* 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 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>
«l&j
(h)
* ‘Certification J‘ means the
official notification by the institution
to the Department
in accordance with
the requirements of this part that a
research project or activity involving
human subjects has been reviewed
and approved by
rdance
(Certification
is required when
the research
is funded by the
Department and not otherwise exempt
in accordance with
§ 46.101(b)).
tVv*v
rwjJ.KuUi'
shall provide written assurance
sni|\f :ii*tprv
(** the
Secret.:: y
that
it
will comply with the requirements set
ford) m these regulations.
lb) The Department will conduct or
fund research covered by these
regu
I at ions only
if the
irisutuiimr nas
an assurance approved as provided
in
this section, and only
if the institution
has certified to the Secretary 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. This
assurance shall at a minimum include:
(DA 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 source of funding. 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 these regulations
applicable to Department-funded
research and
is not applicable to any
research in an exempt category listed
in
§ 46.101.
(2) Designation of one or more
IRBs established in accordance with
the requirements of this subpart, 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 the 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
. ida
\
.
(4)
Written proccduics winch tne
? R H w
i
!
:
fo! low
i
:
; for
c umV- t tr.g
i !
s
initial and continuing review of
research and tor repealing
its findings
and actions to the investigator and the
institution:
(ii) for determining which
project reqjjfc review
o*«tic
iftCii
than annually and which projects
need verification from sources other
than the investigators that no material
changes have occurred since previous
FRB review;
(iii) for insuring prompt
reporting to the IRB of proposed
changes in a research activity, and for
insuring that changes in approved
research, during the period for which
IRB approval has already been given,
may not be initiated without IRB
review and approval except where
necessary to eliminate apparent
immediate hazards to the subject; and
(iv) for insuring prompt reporting
to
the IRB and to the Secretary
1 of
unanticipated problems involving
risks to subjects or others,
(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 these
regulations, and shall be filed in such
form and manner as the Secretary
may prescribe.
(d) The Secretary will evaluate all
assurances submitted in accordance
with these regulations through such
officers and employees of the
Department and such experts or
consultants engaged for this purpose
as the Secretary determines to be
appropriate. The Secretary’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
1 Reports should be Hied with the Office
for Protection from Research Risks, Nation*!
Institutes of Hc*lth. Department of Health
and Human Services, Bcihesda, Maryland
20205
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involved, the appropriate;.*
.-.s of in-
p.vpcv J
:::*t i;i!
a- J
im;
•
review procedures
in
light of the
probable risks, and the
size- and
complexity of the
institution.
(el On the basts of this evaluation,
the Secretary may approve or
disapprove the assurance, or enter
into negotiations to develop an
approvable one. The Secretary may^
limit the period during which any
particular approved assurance or class
of approved assurances shall remain
effective or otherwise condition or
restrict approval.
<0 Within 60 days after (he date of
submission to HHS of an application
or proposal, an institution with an
approved assurance covering the
proposed research shall certify that
the application or proposal has been
reviewed and approved by the IRB.
Other institutions shall certify that the
application or proposal has been
approved by the IRB within 30 days
after receipt of a request for such a
certification from the Department.
If
the certification
is not submitted
within these time limits, the
application or proposal may be
returned to the institution.
§ 46.104
[Reserved]
5 46.105
[Reserved]
5 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’ backgrounds including
consideration of the racial and
cultural backgrounds of members 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
f.oir.p;. !e nee
fit'-, cssr.rs
. review
*
specific research activities,
the IRB
shall
hr*
r^hlr
to ascertain the
acceptability of proposed research
in
terms of institutional commitments
and regulations, applicable law, and
standards of professional conduct and
practice. 7ut IRB shall therefore
include persons knowledgeable
in
these areas.
If an IRB regularly
reviews research that involves a
vulnerable category of subjects,
including but not limited to subjects
covered by other subparts of this part,
the IRB shall include one or more
individuals who are primarily
concerned with the welfare of these
subjects.
(b) No IRB may consist entirely of
men or entirely of women, or entirely
of members of one profession.
(c) Each IRB shall include ai least
one member whose primary concerns
are in nonscientific areas; for
example: lawyers, ethicists, members
of the clergy.
(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
participating 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.
(0 An IRB may,
in
its discretion,
invite individuals with competence in
special areas to assist in the review of
complex issues which require
expertise beyond or in addition to that
available on the IRB. These
individuals may not vote with the
IRB.
5 46.108
IRB functions and
operations.
In order to fulfill the requirements
of these regulations each IRB shall:
(a) Follow written procedures as
provided
in
§ 46.103(b)(4).
Page 7
Except wh-.n
ar, expedite
rex icw priKcdure
is used (see
§ 46.1 10), review proposed research
ai convened meetings
at which a
majority of the members of the IRB
aa* 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.
(c) Be responsible for reporting
to
the appropriate institutional officials
and the Secretary
1 any serious or
continuing noncompliance by
investigators with the requirements
and determinations of the IRB.
5 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 these regulations.
(b) An IRB shall require that
information given to subjects as part
of informed consent is in accordance
with
§ 46,
1 16. The IRB may require
that information,
in addition to that
specifically mentioned in
§ 46,116,
be given to the subjects when in the
IRB
s judgment the information
would 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 d 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
1 Repons should be
filed with the Office
for Protection from Research Risks. National
Institutes ot
Health, Department of Health
and Human Services. Ucthesda. Maryland
2O?0S
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