!"#$ "& '$#$()* +$,-*).

/"01

23245 67
89:43! ;54'<+5
=$>)(.?$0. "& @$)*.A )0# @-?)0 B$(C/D$1
8<+2 6E
8+F25!23FG F' @9H<G B9:I5!2B



Reised January 15, 2009
Lectie July 14, 2009

B9:8<+2 <J
:)1/D @@B 8"*/DK &"( 8(".$DL
./"0 "& @-?)0 +$1$)(DA
B-MN$D.1

B$DO
46.101 1o what does this policy apply

46.102 Deinitions.

46.103 Assuring compliance with this
policy-research conducted or
supported by any lederal Depart-
ment or Agency.

46.104- |Resered|
46.106

46.10 IRB membership.

46.108 IRB unctions and operations.

46.109 IRB reiew o research.

46.110 Lxpedited reiew procedures or
certain kinds o research inoling
no more than minimal risk, and or
minor changes in approed re-
search.

46.111 Criteria or IRB approal o
research.

46.112 Reiew by institution.

46.113 Suspension or termination o
IRB approal o research.

46.114 Cooperatie research.

46.115 IRB records.

46.116 General requirements or in-
ormed consent.

46.11 Documentation o inormed
consent.

46.118 Applications and proposals lack-
ing deinite plans or inolement
o human subjects.

46.119 Research undertaken without
the intention o inoling human
subjects.

46.120 Laluation and disposition o
applications and proposals or re-
search to be conducted or sup-
ported by a lederal Department or
Agency.

46.121 |Resered|

46.122 Use o lederal unds.

46.123 Larly termination o research
support: Laluation o applica-
tions and proposals.

46.124 Conditions.




B9:8<+2 :J
<##/./"0)* 8(".$D./"01 &"(
8($,0)0. ;"?$0P @-?)0 '$L
.-1$1 )0# G$"0).$1 30C"*C$#
/0 +$1$)(DA

B$DO
46.201 1o what do these regulations
apply

46.202 Deinitions.

46.203 Duties o IRBs in connection
with research inoling pregnant
women, etuses, and neonates.

46.204 Research inoling pregnant
women or etuses.

46.205 Research inoling neonates.

46.206 Research inoling, ater deli-
ery, the placenta, the dead etus or
etal material.

46.20 Research not otherwise appro-
able which presents an opportunity
to understand, preent, or alleiate
a serious problem aecting the
health or welare o pregnant
women, etuses, or neonates.




B9:8<+2 !J
<##/./"0)* 8(".$D./"01
8$(.)/0/0, ." :/"?$#/D)* )0#
:$A)C/"()* +$1$)(DA 30C"*CL
/0,
8(/1"0$(1 )1 B-MN$D.1

B$DO
46.301 Applicability.

46.302 Purpose.

46.303 Deinitions.

46.304 Composition o Institutional
Reiew Boards where prisoners
are inoled.

46.305 Additional duties o the Insti-
tutional Reiew Boards where
prisoners are inoled.

46.306 Permitted research inoling
prisoners.

































B9:8<+2 =J
<##/./"0)* 8(".$D./"01
&"( !A/*#($0 30C"*C$# )1 B-ML
N$D.1
/0 +$1$)(DA

B$DO
46.401 1o what do these regulations
apply

46.402 Deinitions.

46.403 IRB duties.

46.404 Research not inoling greater
than minimal risk.

46.405 Research inoling greater
than minimal risk but presenting
the prospect o direct beneit to
the indiidual subjects.

46.406 Research inoling greater
than minimal risk and no pros-
pect o direct beneit to indiid-
ual subjects, but likely to yield
generalizable knowledge about
the subject`s disorder or condi-
tion.

46.40 Research not otherwise ap-
proable which presents an op-
portunity to understand, preent,
or alleiate a serious problem
aecting the health or welare o
children.

46.408 Requirements or permission
by parents or guardians and or
assent by children.

46.409 \ards.

Authority: 5 U.S.C. 301, 42 U.S.C. 289
,a,.

.











B9:8<+2 5 J
+$,/1.()./"0 "& 301./.-./"0)*
+$C/$Q :")(#1

Sec.
46.501 \hat IRBs must be registered
46.502 \hat inormation must be
proided when registering an
IRB
46.503 \hen must an IRB be regis-
tered
46.504 low must an IRB be regis-
tered
46.505 \hen must IRB registration
inormation be renewed or up-
dated










Lditorial Note: 1he Department o
lealth and luman Serices issued a
notice o waier regarding the require-
ments set orth in part 46, relating to
protection o human subjects, as they
pertain to demonstration projects,
approed under section 1115 o the
Social Security Act, which test the use
o cost-sharing, such as deductibles,
copayment and coinsurance, in the
Medicaid program. lor urther inor-
mation see 4 lR 9208, Mar. 4, 1982.
2 45 ClR 46


B9:8<+2 <
:)1/D @@B 8"*/DK &"( 8(".$D./"0
"& @-?)0 +$1$)(DA B-MN$D.1

<-.A"(/.KR 5 U.S.C. 301, 42 U.S.C. 289,
42 U.S.C. 300-1,b,.

B"-(D$R 56 lR 28012, 28022, June 18, 1991,
unless otherwise noted.

S6EOTUT 2" QA). #"$1 .A/1 >"*/DK )>>*KV
,a, Lxcept as proided in paragraph ,b, o
this section, this policy applies to all research
inoling human subjects conducted, sup-
ported or otherwise subject to regulation by
any ederal department or agency which
takes appropriate administratie action to
make the policy applicable to such research.
1his includes research conducted by ederal
ciilian employees or military personnel,
except that each department or agency head
may adopt such procedural modiications as
may be appropriate rom an administratie
standpoint. It also includes research con-
ducted, supported, or otherwise subject to
regulation by the ederal goernment outside
the United States.
,1, Research that is conducted or sup-
ported by a ederal department or agency,
whether or not it is regulated as deined in
46.102,e,, must comply with all sections
o this policy.
,2, Research that is neither conducted nor
supported by a ederal department or
agency but is subject to regulation as de-
ined in 46.102,e, must be reiewed and
approed, in compliance with 46.101,
46.102, and 46.10 through 46.11 o
this policy, by an institutional reiew
board ,IRB, that operates in accordance
with the pertinent requirements o this
policy.
,b, Unless otherwise required by department
or agency heads, research actiities in which
the only inolement o human subjects will
be in one or more o the ollowing catego-
ries are exempt rom this policy:
,1, Research conducted in established or
commonly accepted educational settings,
inoling normal educational practices,
such as ,i, research on regular and special
education instructional strategies, or ,ii,
research on the eectieness o or the
comparison among instructional tech-
niques, curricula, or classroom manage-
ment methods.
,2, Research inoling the use o educa-
tional tests ,cognitie, diagnostic, aptitude,
achieement,, surey procedures, inter-
iew procedures or obseration o public
behaior, unless: ,i, inormation obtained
is recorded in such manner that human
subjects can be identiied, directly or
through identiiers linked to the subjects,
and ,ii, any disclosure o the human sub-
jects` responses outside the research could
reasonably place the subjects at risk o
criminal or ciil liability or be damaging to
the subjects` inancial standing, employ-
ability, or reputation.
,3, Research inoling the use o educa-
tional tests ,cognitie, diagnostic, aptitude,
achieement,, surey procedures, inter-
iew procedures, or obseration o public
behaior that is not exempt under para-
graph ,b,,2, o this section, i:
,i, the human subjects are elected or ap-
pointed public oicials or candidates or
public oice, or ,ii, ederal statute,s, re-
quire,s, without exception that the coni-
dentiality o the personally identiiable
inormation will be maintained through-
out the research and thereater.
,4, Research inoling the collection or
study o existing data, documents, records,
pathological specimens, or diagnostic
specimens, i these sources are publicly
aailable or i the inormation is recorded
by the inestigator in such a manner that
subjects cannot be identiied, directly or
through identiiers linked to the subjects.
,5, Research and demonstration projects
which are conducted by or subject to the
approal o department or agency heads,
and which are designed to study, ealuate,
or otherwise examine:,i, Public beneit or
serice programs, ,ii, procedures or ob-
taining beneits or serices under those
programs, ,iii, possible changes in or alter-
naties to those programs or procedures,
or ,i, possible changes in methods or
leels o payment or beneits or serices
under those programs.
,6, 1aste and ood quality ealuation and
consumer acceptance studies, ,i, i whole-
some oods without addities are con-
sumed or ,ii, i a ood is consumed that
contains a ood ingredient at or below the
leel and or a use ound to be sae, or
agricultural chemical or enironmental
contaminant at or below the leel ound
to be sae, by the lood and Drug Admini-
stration or approed by the Lniron-
mental Protection Agency or the lood
Saety and Inspection Serice o the U.S.
Department o Agriculture.
,c, Department or agency heads retain inal
judgment as to whether a particular actiity
is coered by this policy.
,d, Department or agency heads may require
that speciic research actiities or classes o
research actiities conducted, supported, or
otherwise subject to regulation by the de-
partment or agency but not otherwise co-
ered by this policy, comply with some or all
o the requirements o this policy.
,e, Compliance with this policy requires
compliance with pertinent ederal laws or
regulations which proide additional protec-
tions or human subjects.
,, 1his policy does not aect any state or
local laws or regulations which may other-
wise be applicable and which proide addi-
tional protections or human subjects.
,g, 1his policy does not aect any oreign
laws or regulations which may otherwise be
applicable and which proide additional
protections to human subjects o research.
h, \hen research coered by this policy
takes place in oreign countries, procedures
normally ollowed in the oreign countries
to protect human subjects may dier rom
those set orth in this policy. |An example is
a oreign institution which complies with
guidelines consistent with the \orld Medi-
cal Assembly Declaration ,Declaration o
lelsinki amended 1989, issued either by
soereign states or by an organization whose
unction or the protection o human re-
search subjects is internationally recognized.|
In these circumstances, i a department or
agency head determines that the procedures
prescribed by the institution aord protec-
tions that are at least equialent to those
proided in this policy, the department or
agency head may approe the substitution o
the oreign procedures in lieu o the proce-
dural requirements proided in this policy.
Lxcept when otherwise required by statute,
Lxecutie Order, or the department or
agency head, notices o these actions as they
occur will be published in the lLDLRAL
RLGIS1LR or will be otherwise published
as proided in department or agency proce-
dures.

45 ClR 46 3


,i, Unless otherwise required by law, depart-
ment or agency heads may waie the appli-
cability o some or all o the proisions o
this policy to speciic research actiities or
classes o research actiities otherwise co-
ered by this policy. Lxcept when otherwise
required by statute or Lxecutie Order, the
department or agency head shall orward
adance notices o these actions to the O-
ice or luman Research Protections, De-
partment o lealth and luman Serices
,llS,, or any successor oice, and shall
also publish them in the lLDLRAL RLG-
IS1LR or in such other manner as proided
in department or agency procedures.
1

|56 lR 28012, 28022, June 18, 1991, 56 lR 2956, June
28, 1991, as amended at 0 lR 36328, June 23, 2005|

S6EOTUW =$&/0/./"01O
,a, !"#$%&'"(& *% $+"(,- ."$/ means the head
o any ederal department or agency and any
other oicer or employee o any department
or agency to whom authority has been dele-
gated.
,b, 0(1&2&3&2*( means any public or priate
entity or agency ,including ederal, state, and
other agencies,.
,c, 4"+$55- $3&.*%26"/ %"#%"1"(&$&27" means an
indiidual or judicial or other body author-
ized under applicable law to consent on
behal o a prospectie subject to the sub-
ject`s participation in the procedure,s, in-
oled in the research.
,d, 8"1"$%,. means a systematic inestigation,
including research deelopment, testing and
ealuation, designed to deelop or contrib-
ute to generalizable knowledge. Actiities
which meet this deinition constitute re-
search or purposes o this policy, whether
or not they are conducted or supported un-
der a program which is considered research
or other purposes. lor example, some dem-
onstration and serice programs may include
research actiities.
,e, 8"1"$%,. 139:",& &* %"+35$&2*(, and similar
terms are intended to encompass those re-
search actiities or which a ederal depart-
ment or agency has speciic responsibility
or regulating as a research actiity ,or ex-
ample, Inestigational New Drug require-
ments administered by the lood and Drug
Administration,. It does not include research
actiities which are incidentally regulated by
a ederal department or agency solely as part
o the department`s or agency`s broader
responsibility to regulate certain types o
actiities whether research or non-research
in nature ,or example, \age and lour re-
quirements administered by the Department
o Labor,.
,, ;3'$( 139:",& means a liing indiidual
about whom an inestigator ,whether pro-
essional or student, conducting research
obtains
,1, Data through interention or interac-
tion with the indiidual, or
,2, Identiiable priate inormation.
0(&"%7"(&2*( includes both physical procedures
by which data are gathered ,or example,
enipuncture, and manipulations o the sub-
ject or the subject`s enironment that are
perormed or research purposes. Interac-
tion includes communication or interper-
sonal contact between inestigator and sub-
ject. Priate inormation includes inorma-
tion about behaior that occurs in a context
in which an indiidual can reasonably expect
that no obseration or recording is taking
place, and inormation which has been pro-
ided or speciic purposes by an indiidual
and which the indiidual can reasonably
expect will not be made public ,or example,
a medical record,.
<%27$&" 2(=*%'$&2*( must be indiidually identi-
iable ,i.e., the identity o the subject is or
may readily be ascertained by the inestiga-
tor or associated with the inormation, in
order or obtaining the inormation to con-
stitute research inoling human subjects.
,g, 08> means an institutional reiew board
established in accord with and or the pur-
poses expressed in this policy.
,h, 08> $##%*7$5 means the determination o
the IRB that the research has been reiewed
and may be conducted at an institution
within the constraints set orth by the IRB
and by other institutional and ederal re-
quirements.
,i, ?2(2'$5 %21@ means that the probability
and magnitude o harm or discomort antici-
pated in the research are not greater in and
o themseles than those ordinarily encoun-
tered in daily lie or during the perormance
o routine physical or psychological exami-
nations or tests.
h, \hen research coered by this policy
takes place in oreign countries, procedures
normally ollowed in the oreign countries
to protect human subjects may dier rom
those set orth in this policy. |An example is
a oreign institution which complies with
guidelines consistent with the \orld Medi-
cal Assembly Declaration ,Declaration o
lelsinki amended 1989, issued either by
soereign states or by an organization whose
unction or the protection o human re-
search subjects is internationally recognized.|
In these circumstances, i a department or
agency head determines that the procedures
prescribed by the institution aord protec-
tions that are at least equialent to those
proided in this policy, the department or
agency head may approe the substitution o
the oreign procedures in lieu o the proce-
dural requirements proided in this policy.
Lxcept when otherwise required by statute,
Lxecutie Order, or the department or
agency head, notices o these actions as they
occur will be published in the lLDLRAL
RLGIS1LR or will be otherwise published
as proided in department or agency proce-
dures.

1
Institutions with llS-approed assurances on ile will abide by proisions o 1itle 45 ClR part 46 subparts A-D. Some o the other departments and agencies hae incor-
porated all proisions o 1itle 45 ClR part 46 into their policies and procedures as well. loweer, the exemptions at 45 ClR 46.101,b, do not apply to research inoling
prisoners, subpart C. 1he exemption at 45 ClR 46.101,b,,2,, or research inoling surey or interiew procedures or obseration o public behaior, does not apply to
research with children, subpart D, except or research inoling obserations o public behaior when the inestigator,s, do not participate in the actiities being obsered.
4 45 ClR 46


S6EOTUX <11-(/0, D"?>*/)0D$ Q/.A .A/1
>"*/DK LL ($1$)(DA D"0#-D.$# "( 1->L
>"(.$# MK )0K '$#$()* =$>)(.?$0.
"( <,$0DKO
,a, Lach institution engaged in research
which is coered by this policy and which is
conducted or supported by a ederal depart-
ment or agency shall proide written assur-
ance satisactory to the department or
agency head that it will comply with the
requirements set orth in this policy. In lieu
o requiring submission o an assurance,
indiidual department or agency heads shall
accept the existence o a current assurance,
appropriate or the research in question, on
ile with the Oice or luman Research
Protections, llS, or any successor oice,
and approed or ederalwide use by that
oice. \hen the existence o an llS-
approed assurance is accepted in lieu o
requiring submission o an assurance, re-
ports ,except certiication, required by this
policy to be made to department and agency
heads shall also be made to the Oice or
luman Research Protections, llS, or any
successor oice.
,b, Departments and agencies will conduct
or support research coered by this policy
only i the institution has an assurance ap-
proed as proided in this section, and only
i the institution has certiied to the depart-
ment or agency head that the research has
been reiewed and approed by an IRB pro-
ided or in the assurance, and will be sub-
ject to continuing reiew by the IRB. Assur-
ances applicable to ederally supported or
conducted research shall at a minimum in-
clude:
,1,A statement o principles goerning the
institution in the discharge o its responsi-
bilities or protecting the rights and wel-
are o human subjects o research con-
ducted at or sponsored by the institution,
regardless o whether the research is sub-
ject to lederal regulation. 1his may in-
clude an appropriate existing code, decla-
ration, or statement o ethical principles,
or a statement ormulated by the institu-
tion itsel. 1his requirement does not pre-
empt proisions o this policy applicable
to department- or agency-supported or
regulated research and need not be appli-
cable to any research exempted or waied
under 46.101,b, or ,i,.
,2,Designation o one or more IRBs estab-
lished in accordance with the requirements
o this policy, and or which proisions are
made or meeting space and suicient
sta to support the IRB's reiew and re-
cordkeeping duties.
,3,A list o IRB members identiied by
name, earned degrees, representatie ca-
pacity, indications o experience such as
board certiications, licenses, etc., sui-
cient to describe each member's chie an-
ticipated contributions to IRB delibera-
tions, and any employment or other rela-
tionship between each member and the
institution, or example: ull-time em-
ployee, part-time employee, member o
goerning panel or board, stockholder,
paid or unpaid consultant. Changes in IRB
membership shall be reported to the de-
partment or agency head, unless in accord
with 46.103,a, o this policy, the exis-
tence o an llS-approed assurance is
accepted. In this case, change in IRB
membership shall be reported to the O-
ice or luman Research Protections,
llS, or any successor oice.
,4,\ritten procedures which the IRB will
ollow ,i, or conducting its initial and
continuing reiew o research and or re-
porting its indings and actions to the in-
estigator and the institution, ,ii, or deter-
mining which projects require reiew more
oten than annually and which projects
need eriication rom sources other than
the inestigators that no material changes
hae occurred since preious IRB reiew,
and ,iii, or ensuring prompt reporting to
the IRB o proposed changes in a research
actiity, and or ensuring that such
changes in approed research, during the
period or which IRB approal has already
been gien, may not be initiated without
IRB reiew and approal except when
necessary to eliminate apparent immediate
hazards to the subject.
,5,\ritten procedures or ensuring
prompt reporting to the IRB, appropriate
institutional oicials, and the department
or agency head o ,i, any unanticipated
problems inoling risks to subjects or
others or any serious or continuing non-
compliance with this policy or the require-
ments or determinations o the IRB, and
,ii, any suspension or termination o IRB
approal.
,c, 1he assurance shall be executed by an
indiidual authorized to act or the institu-
tion and to assume on behal o the institu-
tion the obligations imposed by this policy
and shall be iled in such orm and manner
as the department or agency head prescribes.
,d, 1he department or agency head will
ealuate all assurances submitted in accor-
dance with this policy through such oicers
and employees o the department or agency
and such experts or consultants engaged or
this purpose as the department or agency
head determines to be appropriate. 1he de-
partment or agency head's ealuation will
take into consideration the adequacy o the
proposed IRB in light o the anticipated
scope o the institution's research actiities
and the types o subject populations likely to
be inoled, the appropriateness o the pro-
posed initial and continuing reiew proce-
dures in light o the probable risks, and the
size and complexity o the institution.
,e, On the basis o this ealuation, the de-
partment or agency head may approe or
disapproe the assurance, or enter into ne-
gotiations to deelop an approable one.
1he department or agency head may limit
the period during which any particular ap-
proed assurance or class o approed assur-
ances shall remain eectie or otherwise
condition or restrict approal.
,, Certiication is required when the re-
search is supported by a ederal department
or agency and not otherwise exempted or
waied under 46.101,b, or ,i,. An institu-
tion with an approed assurance shall certiy
that each application or proposal or re-
search coered by the assurance and by
46.103 o this Policy has been reiewed and
approed by the IRB. Such certiication
must be submitted with the application or
proposal or by such later date as may be
prescribed by the department or agency to
which the application or proposal is submit-
ted. Under no condition shall research co-
ered by 46.103 o the Policy be supported
prior to receipt o the certiication that the
research has been reiewed and approed by
the IRB. Institutions without an approed
assurance coering the research shall certiy
within 30 days ater receipt o a request or
such a certiication rom the department or
agency, that the application or proposal has
been approed by the IRB. I the certiica-
tion is not submitted within these time lim-
its, the application or proposal may be re-
turned to the institution.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, 56 lR 2956, June
28, 1991, as amended at 0 lR 36328, June 23, 2005|
SS6EOTU6LL6EOTUE |Resered|






45 ClR 46 5


S6EOTUY 3+: ?$?M$(1A/>O
,a, Lach IRB shall hae at least ie mem-
bers, with arying backgrounds to promote
complete and adequate reiew o research
actiities commonly conducted by the insti-
tution. 1he IRB shall be suiciently quali-
ied through the experience and expertise o
its members, and the diersity o the mem-
bers, including consideration o race, gender,
and cultural backgrounds and sensitiity to
such issues as community attitudes, to pro-
mote respect or its adice and counsel in
saeguarding the rights and welare o hu-
man subjects. In addition to possessing the
proessional competence necessary to reiew
speciic research actiities, the IRB shall be
able to ascertain the acceptability o pro-
posed research in terms o institutional com-
mitments and regulations, applicable law,
and standards o proessional conduct and
practice. 1he IRB shall thereore include
persons knowledgeable in these areas. I an
IRB regularly reiews research that inoles
a ulnerable category o subjects, such as
children, prisoners, pregnant women, or
handicapped or mentally disabled persons,
consideration shall be gien to the inclusion
o one or more indiiduals who are knowl-
edgeable about and experienced in working
with these subjects.
,b, Lery nondiscriminatory eort will be
made to ensure that no IRB consists entirely
o men or entirely o women, including the
institution's consideration o qualiied per-
sons o both sexes, so long as no selection is
made to the IRB on the basis o gender. No
IRB may consist entirely o members o one
proession.
,c, Lach IRB shall include at least one mem-
ber whose primary concerns are in scientiic
areas and at least one member whose pri-
mary concerns are in nonscientiic areas.
,d, Lach IRB shall include at least one mem-
ber who is not otherwise ailiated with the
institution and who is not part o the imme-
diate amily o a person who is ailiated
with the institution.
,e, No IRB may hae a member participate
in the IRB's initial or continuing reiew o
any project in which the member has a con-
licting interest, except to proide inorma-
tion requested by the IRB.
,, An IRB may, in its discretion, inite indi-
iduals with competence in special areas to
assist in the reiew o issues which require
expertise beyond or in addition to that aail-
able on the IRB. 1hese indiiduals may not
ote with the IRB
S6EOTUZ 3+: &-0D./"01 )0# ">$()./"01O
In order to ulill the requirements o this
policy each IRB shall:
,a, lollow written procedures in the same
detail as described in 46.103,b,,4, and, to
the extent required by, 46.103,b,,5,.
,b, Lxcept when an expedited reiew proce-
dure is used ,see 46.110,, reiew proposed
research at conened meetings at which a
majority o the members o the IRB are
present, including at least one member
whose primary concerns are in nonscientiic
areas. In order or the research to be ap-
proed, it shall receie the approal o a
majority o those members present at the
meeting.
S6EOTU[ 3+: ($C/$Q "& ($1$)(DAO
,a, An IRB shall reiew and hae authority
to approe, require modiications in ,to se-
cure approal,, or disapproe all research
actiities coered by this policy.
,b, An IRB shall require that inormation
gien to subjects as part o inormed con-
sent is in accordance with 46.116. 1he IRB
may require that inormation, in addition to
that speciically mentioned in 46.116, be
gien to the subjects when in the IRB's judg-
ment the inormation would meaningully
add to the protection o the rights and wel-
are o subjects.
,c, An IRB shall require documentation o
inormed consent or may waie documenta-
tion in accordance with 46.11.
,d, An IRB shall notiy inestigators and the
institution in writing o its decision to ap-
proe or disapproe the proposed research
actiity, or o modiications required to se-
cure IRB approal o the research actiity. I
the IRB decides to disapproe a research
actiity, it shall include in its written notiica-
tion a statement o the reasons or its deci-
sion and gie the inestigator an opportunity
to respond in person or in writing.
,e, An IRB shall conduct continuing reiew
o research coered by this policy at inter-
als appropriate to the degree o risk, but
not less than once per year, and shall hae
authority to obsere or hae a third party
obsere the consent process and the re-
search.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|

S6EOTTU 5\>$#/.$# ($C/$Q >("D$#-($1 &"(
D$(.)/0 ]/0#1 "& ($1$)(DA /0C"*C/0, 0"
?"($ .A)0 ?/0/?)* (/1]P )0# &"( ?/0"(
DA)0,$1 /0 )>>("C$# ($1$)(DAO
,a, 1he Secretary, llS, has established, and
published as a Notice in the lLDLRAL
RLGIS1LR, a list o categories o research
that may be reiewed by the IRB through an
expedited reiew procedure. 1he list will be
amended, as appropriate, ater consultation
with other departments and agencies,
through periodic republication by the Secre-
tary, llS, in the lLDLRAL RLGIS1LR.
A copy o the list is aailable rom the O-
ice or luman Research Protections, llS,
or any successor oice.
,b, An IRB may use the expedited reiew
procedure to reiew either or both o the
ollowing:
,1, some or all o the research appearing
on the list and ound by the reiewer,s, to
inole no more than minimal risk,
,2, minor changes in preiously approed
research during the period ,o one year or
less, or which approal is authorized.
Under an expedited reiew procedure, the
reiew may be carried out by the IRB chair-
person or by one or more experienced re-
iewers designated by the chairperson rom
among members o the IRB. In reiewing
the research, the reiewers may exercise all
o the authorities o the IRB except that the
reiewers may not disapproe the research.
A research actiity may be disapproed only
ater reiew in accordance with the non-
expedited procedure set orth in 46.108,b,.
,c, Lach IRB which uses an expedited re-
iew procedure shall adopt a method or
keeping all members adised o research
proposals which hae been approed under
the procedure.
,d, 1he department or agency head may
restrict, suspend, terminate, or choose not to
authorize an institution's or IRB's use o the
expedited reiew procedure.
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|
S6EOTTT !(/.$(/) &"( 3+: )>>("C)* "& ($L
1$)(DAO
,a, In order to approe research coered by
this policy the IRB shall determine that all o
the ollowing requirements are satisied:
,1, Risks to subjects are minimized: ,i, By
using procedures which are consistent
with sound research design and which do
not unnecessarily expose subjects to risk,
and ,ii, wheneer appropriate, by using
procedures already being perormed on
the subjects or diagnostic or treatment
purposes.
6 45 ClR 46


,2, Risks to subjects are reasonable in rela-
tion to anticipated beneits, i any, to sub-
jects, and the importance o the knowl-
edge that may reasonably be expected to
result. In ealuating risks and beneits, the
IRB should consider only those risks and
beneits that may result rom the research
,as distinguished rom risks and beneits o
therapies subjects would receie een i
not participating in the research,. 1he IRB
should not consider possible long-range
eects o applying knowledge gained in
the research ,or example, the possible
eects o the research on public policy, as
among those research risks that all within
the puriew o its responsibility.
,3, Selection o subjects is equitable. In
making this assessment the IRB should
take into account the purposes o the re-
search and the setting in which the re-
search will be conducted and should be
particularly cognizant o the special prob-
lems o research inoling ulnerable
populations, such as children, prisoners,
pregnant women, mentally disabled per-
sons, or economically or educationally
disadantaged persons.
,4, Inormed consent will be sought rom
each prospectie subject or the subject's
legally authorized representatie, in accor-
dance with, and to the extent required by
46.116.
,5, Inormed consent will be appropriately
documented, in accordance with, and to
the extent required by 46.11.
,6, \hen appropriate, the research plan
makes adequate proision or monitoring
the data collected to ensure the saety o
subjects.
,, \hen appropriate, there are adequate
proisions to protect the priacy o sub-
jects and to maintain the conidentiality o
data.
,b, \hen some or all o the subjects are
likely to be ulnerable to coercion or undue
inluence, such as children, prisoners, preg-
nant women, mentally disabled persons, or
economically or educationally disadantaged
persons, additional saeguards hae been
included in the study to protect the rights
and welare o these subjects.
S6EOTTW +$C/$Q MK /01./.-./"0O
Research coered by this policy that has
been approed by an IRB may be subject to
urther appropriate reiew and approal or
disapproal by oicials o the institution.
loweer, those oicials may not approe
the research i it has not been approed by
an IRB.



S6EOTTX B-1>$01/"0 "( .$(?/0)./"0 "&
3+: )>>("C)* "& ($1$)(DAO
An IRB shall hae authority to suspend or
terminate approal o research that is not
being conducted in accordance with the
IRB's requirements or that has been associ-
ated with unexpected serious harm to sub-
jects. Any suspension or termination o ap-
proal shall include a statement o the rea-
sons or the IRB's action and shall be re-
ported promptly to the inestigator, appro-
priate institutional oicials, and the depart-
ment or agency head.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|
S6EOTT6 !"">$()./C$ ($1$)(DAO
Cooperatie research projects are those pro-
jects coered by this policy which inole
more than one institution. In the conduct o
cooperatie research projects, each institu-
tion is responsible or saeguarding the
rights and welare o human subjects and or
complying with this policy. \ith the ap-
proal o the department or agency head, an
institution participating in a cooperatie
project may enter into a joint reiew ar-
rangement, rely upon the reiew o another
qualiied IRB, or make similar arrangements
or aoiding duplication o eort.
S6EOTT7 3+: ($D"(#1O
,a, An institution, or when appropriate an
IRB, shall prepare and maintain adequate
documentation o IRB actiities, including
the ollowing:
,1, Copies o all research proposals re-
iewed, scientiic ealuations, i any, that
accompany the proposals, approed sam-
ple consent documents, progress reports
submitted by inestigators, and reports o
injuries to subjects.
,2, Minutes o IRB meetings which shall
be in suicient detail to show attendance
at the meetings, actions taken by the IRB,
the ote on these actions including the
number o members oting or, against,
and abstaining, the basis or requiring
changes in or disapproing research, and a
written summary o the discussion o con-
troerted issues and their resolution.
,3, Records o continuing reiew actiities.
,4, Copies o all correspondence between
the IRB and the inestigators.
,5, A list o IRB members in the same
detail as described in 46.103,b,,3,.
,6, \ritten procedures or the IRB in the
same detail as described in 46.103,b,,4,
and 46.103,b,,5,.
,, Statements o signiicant new indings
proided to subjects, as required by
46.116,b,,5,.
,b, 1he records required by this policy shall
be retained or at least 3 years, and records
relating to research which is conducted shall
be retained or at least 3 years ater comple-
tion o the research. All records shall be
accessible or inspection and copying by
authorized representaties o the depart-
ment or agency at reasonable times and in a
reasonable manner.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|
S6EOTTE ^$0$()* ($_-/($?$0.1 &"( /0L
&"(?$# D"01$0.O
Lxcept as proided elsewhere in this policy,
no inestigator may inole a human being
as a subject in research coered by this pol-
icy unless the inestigator has obtained the
legally eectie inormed consent o the
subject or the subject's legally authorized
representatie. An inestigator shall seek
such consent only under circumstances that
proide the prospectie subject or the repre-
sentatie suicient opportunity to consider
whether or not to participate and that mini-
mize the possibility o coercion or undue
inluence. 1he inormation that is gien to
the subject or the representatie shall be in
language understandable to the subject or
the representatie. No inormed consent,
whether oral or written, may include any
exculpatory language through which the
subject or the representatie is made to
waie or appear to waie any o the subject's
legal rights, or releases or appears to release
the inestigator, the sponsor, the institution
or its agents rom liability or negligence.
,a, Basic elements o inormed consent.
Lxcept as proided in paragraph ,c, or ,d, o
this section, in seeking inormed consent the
ollowing inormation shall be proided to
each subject:
,1, A statement that the study inoles
research, an explanation o the purposes
o the research and the expected duration
o the subject's participation, a description
o the procedures to be ollowed, and
identiication o any procedures which are
experimental,
,2, A description o any reasonably ore-
seeable risks or discomorts to the subject,
,3, A description o any beneits to the
subject or to others which may reasonably
be expected rom the research,
,4, A disclosure o appropriate alternatie
procedures or courses o treatment, i any,
that might be adantageous to the subject,
,5, A statement describing the extent, i
any, to which conidentiality o records
identiying the subject will be maintained,
45 ClR 46


,6, lor research inoling more than mini-
mal risk, an explanation as to whether any
compensation and an explanation as to
whether any medical treatments are aail-
able i injury occurs and, i so, what they
consist o, or where urther inormation
may be obtained,
,, An explanation o whom to contact or
answers to pertinent questions about the
research and research subjects' rights, and
whom to contact in the eent o a re-
search-related injury to the subject, and
,8, A statement that participation is olun-
tary, reusal to participate will inole no
penalty or loss o beneits to which the
subject is otherwise entitled, and the sub-
ject may discontinue participation at any
time without penalty or loss o beneits to
which the subject is otherwise entitled.
,b, Additional elements o inormed con-
sent. \hen appropriate, one or more o the
ollowing elements o inormation shall also
be proided to each subject:
,1, A statement that the particular treat-
ment or procedure may inole risks to
the subject ,or to the embryo or etus, i
the subject is or may become pregnant,
which are currently unoreseeable,
,2, Anticipated circumstances under which
the subject's participation may be termi-
nated by the inestigator without regard to
the subject's consent,
,3, Any additional costs to the subject that
may result rom participation in the re-
search,
,4, 1he consequences o a subject's deci-
sion to withdraw rom the research and
procedures or orderly termination o par-
ticipation by the subject,
,5, A statement that signiicant new ind-
ings deeloped during the course o the
research which may relate to the subject's
willingness to continue participation will
be proided to the subject, and
,6, 1he approximate number o subjects
inoled in the study.
,c, An IRB may approe a consent proce-
dure which does not include, or which alters,
some or all o the elements o inormed
consent set orth aboe, or waie the re-
quirement to obtain inormed consent pro-
ided the IRB inds and documents that:
,1, 1he research or demonstration project
is to be conducted by or subject to the
approal o state or local goernment oi-
cials and is designed to study, ealuate, or
otherwise examine: ,i, public beneit or
serice programs, ,ii, procedures or ob-
taining beneits or serices under those
programs, ,iii, possible changes in or alter-
naties to those programs or procedures,
or ,i, possible changes in methods or
leels o payment or beneits or serices
under those programs, and
,2, 1he research could not practicably be
carried out without the waier or altera-
tion.
,d, An IRB may approe a consent proce-
dure which does not include, or which alters,
some or all o the elements o inormed
consent set orth in this section, or waie
the requirements to obtain inormed con-
sent proided the IRB inds and documents
that:
1, 1he research inoles no more than mini-
mal risk to the subjects,
,2, 1he waier or alteration will not ad-
ersely aect the rights and welare o the
subjects,
,3, 1he research could not practicably be
carried out without the waier or alteration,
and
,4, \heneer appropriate, the subjects will
be proided with additional pertinent inor-
mation ater participation.
,e, 1he inormed consent requirements in
this policy are not intended to preempt any
applicable ederal, state, or local laws which
require additional inormation to be dis-
closed in order or inormed consent to be
legally eectie.
,, Nothing in this policy is intended to limit
the authority o a physician to proide emer-
gency medical care, to the extent the physi-
cian is permitted to do so under applicable
ederal, state, or local law.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|
S6EOTTY ="D-?$0.)./"0 "& /0&"(?$# D"0L
1$0.O
,a, Lxcept as proided in paragraph ,c, o
this section, inormed consent shall be docu-
mented by the use o a written consent orm
approed by the IRB and signed by the sub-
ject or the subject's legally authorized repre-
sentatie. A copy shall be gien to the per-
son signing the orm.
,b, Lxcept as proided in paragraph ,c, o
this section, the consent orm may be either
o the ollowing:
,1, A written consent document that em-
bodies the elements o inormed consent
required by 46.116. 1his orm may be read
to the subject or the subject's legally author-
ized representatie, but in any eent, the
inestigator shall gie either the subject or
the representatie adequate opportunity to
read it beore it is signed, or
,2, A short orm written consent document
stating that the elements o inormed con-
sent required by 46.116 hae been pre-
sented orally to the subject or the subject's
legally authorized representatie. \hen this
method is used, there shall be a witness to
the oral presentation. Also, the IRB shall
approe a written summary o what is to be
said to the subject or the representatie.
Only the short orm itsel is to be signed by
the subject or the representatie. loweer,
the witness shall sign both the short orm
and a copy o the summary, and the person
actually obtaining consent shall sign a copy
o the summary. A copy o the summary
shall be gien to the subject or the represen-
tatie, in addition to a copy o the short
orm.
,c, An IRB may waie the requirement or
the inestigator to obtain a signed consent
orm or some or all subjects i it inds ei-
ther:
,1, 1hat the only record linking the subject
and the research would be the consent docu-
ment and the principal risk would be poten-
tial harm resulting rom a breach o coni-
dentiality. Lach subject will be asked
whether the subject wants documentation
linking the subject with the research, and the
subject's wishes will goern, or
,2, 1hat the research presents no more than
minimal risk o harm to subjects and in-
oles no procedures or which written con-
sent is normally required outside o the re-
search context.
In cases in which the documentation re-
quirement is waied, the IRB may require
the inestigator to proide subjects with a
written statement regarding the research.
,Approed by the Oice o Management and Budget
under Control Number 0990-0260.,
|56 lR 28012, 28022, June 18, 1991, as amended at 0
lR 36328, June 23, 2005|
S6EOTTZ <>>*/D)./"01 )0# >(">"1)*1 *)D]L
/0, #$&/0/.$ >*)01 &"( /0C"*C$?$0. "&
A-?)0 1-MN$D.1O
Certain types o applications or grants, co-
operatie agreements, or contracts are sub-
mitted to departments or agencies with the
knowledge that subjects may be inoled
within the period o support, but deinite
plans would not normally be set orth in the
application or proposal. 1hese include ac-
tiities such as institutional type grants when
selection o speciic projects is the institu-
tion's responsibility, research training grants
in which the actiities inoling subjects
remain to be selected, and projects in which
human subjects' inolement will depend
upon completion o instruments, prior ani-
mal studies, or puriication o compounds.
1hese applications need not be reiewed by
an IRB beore an award may be made. low-
eer, except or research exempted or
waied under 46.101,b, or ,i,, no human
subjects may be inoled in any project sup-
ported by these awards until the project has
been reiewed and approed by the IRB, as
proided in this policy, and certiication
submitted, by the institution, to the depart-
ment or agency.
8 45 ClR 46


S6EOTT[ +$1$)(DA -0#$(.)]$0 Q/.A"-. .A$
/0.$0./"0 "& /0C"*C/0, A-?)0 1-ML
N$D.1O
In the eent research is undertaken without
the intention o inoling human subjects,
but it is later proposed to inole human
subjects in the research, the research shall
irst be reiewed and approed by an IRB,
as proided in this policy, a certiication
submitted, by the institution, to the depart-
ment or agency, and inal approal gien to
the proposed change by the department or
agency.
S6EOTWU 5C)*-)./"0 )0# #/1>"1/./"0 "&
)>>*/D)./"01 )0# >(">"1)*1 &"( ($L
1$)(DA ." M$ D"0#-D.$# "( 1->>"(.$#
MK ) '$#$()* =$>)(.?$0. "( <,$0DKO
,a, 1he department or agency head will
ealuate all applications and proposals in-
oling human subjects submitted to the
department or agency through such oicers
and employees o the department or agency
and such experts and consultants as the de-
partment or agency head determines to be
appropriate. 1his ealuation will take into
consideration the risks to the subjects, the
adequacy o protection against these risks,
the potential beneits o the research to the
subjects and others, and the importance o
the knowledge gained or to be gained.
,b, On the basis o this ealuation, the de-
partment or agency head may approe or
disapproe the application or proposal, or
enter into negotiations to deelop an ap-
proable one.
S6EOTWT |Resered|
S6EOTWW 91$ "& '$#$()* &-0#1O
lederal unds administered by a department
or agency may not be expended or research
inoling human subjects unless the require-
ments o this policy hae been satisied.
46.123 Larly termination o research sup-
port: Laluation o applications and propos-
als.
,a, 1he department or agency head may
require that department or agency support
or any project be terminated or suspended
in the manner prescribed in applicable pro-
gram requirements, when the department or
agency head inds an institution has materi-
ally ailed to comply with the terms o this
policy.
,b, In making decisions about supporting or
approing applications or proposals coered
by this policy the department or agency head
may take into account, in addition to all
other eligibility requirements and program
criteria, actors such as whether the appli-
cant has been subject to a termination or
suspension under paragraph ,a, o this sec-
tion and whether the applicant or the person
or persons who would direct or has,hae
directed the scientiic and technical aspects
o an actiity has,hae, in the judgment o
the department or agency head, materially
ailed to discharge responsibility or the pro-
tection o the rights and welare o human
subjects ,whether or not the research was
subject to ederal regulation,.
S6EOTW6 !"0#/./"01O
\ith respect to any research project or any
class o research projects the department or
agency head may impose additional condi-
tions prior to or at the time o approal
when in the judgment o the department or
agency head additional conditions are neces-
sary or the protection o human subjects.

B-M>)(. :
<##/./"0)* 8(".$D./"01 &"( 8($,L
0)0. ;"?$0P @-?)0 '$.-1$1
)0# G$"0).$1 30C"*C$# /0 +$L
1$)(DA
Source: 66 lR 568, No. 13, 2001, unless otherwise
noted.
S6EOWUT 2" QA). #" .A$1$ ($,-*)./"01
)>>*KV
,a, Lxcept as proided in paragraph ,b, o
this section, this subpart applies to all re-
search inoling pregnant women, human
etuses, neonates o uncertain iability, or
noniable neonates conducted or supported
by the Department o lealth and luman
Serices ,DllS,. 1his includes all research
conducted in DllS acilities by any person
and all research conducted in any acility by
DllS employees.
,b, 1he exemptions at 46.101,b,,1, through
,6, are applicable to this subpart.
,c, 1he proisions o 46.101,c, through ,i,
are applicable to this subpart. Reerence to
State or local laws in this subpart and in
46.101,, is intended to include the laws o
ederally recognized American Indian and
Alaska Natie 1ribal Goernments.
,d, 1he requirements o this subpart are in
addition to those imposed under the other
subparts o this part.
S6EOWUW =$&/0/./"01O
1he deinitions in 46.102 shall be applica-
ble to this subpart as well. In addition, as
used in this subpart:
,a, Dead etus means a etus that exhibits
neither heartbeat, spontaneous respiratory
actiity, spontaneous moement o olun-
tary muscles, nor pulsation o the umbilical
cord.
,b, Deliery means complete separation o
the etus rom the woman by expulsion or
extraction or any other means.
,c, letus means the product o conception
rom implantation until deliery.
,d, Neonate means a newborn.
,e, Noniable neonate means a neonate ater
deliery that, although liing, is not iable.
,, Pregnancy encompasses the period o
time rom implantation until deliery. A
woman shall be assumed to be pregnant i
she exhibits any o the pertinent presump-
tie signs o pregnancy, such as missed men-
ses, until the results o a pregnancy test are
negatie or until deliery.
,g, Secretary means the Secretary o lealth
and luman Serices and any other oicer
or employee o the Department o lealth
and luman Serices to whom authority has
been delegated.
,h, Viable, as it pertains to the neonate,
means being able, ater deliery, to surie
,gien the beneit o aailable medical ther-
apy, to the point o independently maintain-
ing heartbeat and respiration. 1he Secretary
may rom time to time, taking into account
medical adances, publish in the lLDLRAL
RLGIS1LR guidelines to assist in determin-
ing whether a neonate is iable or purposes
o this subpart. I a neonate is iable then it
may be included in research only to the ex-
tent permitted and in accordance with the
requirements o subparts A and D o this
part.
S6EOWUX =-./$1 "& 3+:1 /0 D"00$D./"0
Q/.A ($1$)(DA /0C"*C/0, >($,0)0.
Q"?$0P &$.-1$1P )0# 0$"0).$1O
In addition to other responsibilities assigned
to IRBs under this part, each IRB shall re-
iew research coered by this subpart and
approe only research which satisies the
conditions o all applicable sections o this
subpart and the other subparts o this part.
S6EOWU6 +$1$)(DA /0C"*C/0, >($,0)0.
Q"?$0 "( &$.-1$1O
Pregnant women or etuses may be inoled
in research i all o the ollowing conditions
are met:
,a, \here scientiically appropriate, preclini-
cal studies, including studies on pregnant
animals, and clinical studies, including stud-
ies on nonpregnant women, hae been con-
ducted and proide data or assessing poten-
tial risks to pregnant women and etuses,
45 ClR 46 9