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pn-iod of funding, but definite plans
*
'would not normally be set forth in the
|
application or proposal. These
include activities such as institutional
type grams (including bloc: grams)
where selection of specific projects is
the institution's responsibility;
research training grants where the
activities involving subjects remain to
be selected; and projects in which
human subjects’ involvement will
depend upon completion of
instruments, prior animal studies, or
purification of compounds. These
applications need not be reviewed by
an IRB before an award may be
nude. However, except for research
described in
§ 46. 101(b), no human
subjects may be involved in any
project supported by these awards
until the project has been reviewed
and approved by the IRB,
as; provided
in these regulations, and certification
submitted to the Department.
§46.119
Research undertaken
without the intention of involving
human subjects.
In the event research (conducted or
funded by the Department) is
undertaken without the intention of
involving human subjects, but
it
is
later proposed to use human subjects
in the research, the research shall
first
be reviewed arid approved by an IRB,
as provided
in these regulations,
a
certification submitted
to the
Dep.ii (merit, and
linal approval given
to
tiie proposed change by the
Department.
S' 46,120
Evaluation and
disposition uf applications and
proposals.
(ai The Secretary will evaluate
all
applications and proposals involving
human subjects submitted
to the
Department through such officers and
employees ot the Department and
siidi experts and consultants as the
Secretary determines to be
appropriate.
This evaluation will take
into consideration the risks to the
subjects, the adequacy of protection
against these risks, the potential
benefits of the proposed research to
the subjects and others, and the
importance of the knowledge to be
gained.
(b) On the basis of this evaluation,
the Secretary tnay approve or
disapprove the application or
proposal, or enter into negotiations to
develop an approvable one.
I 46.121
Investigational new drug
or device 30-day delay requirement.
When an institution
is required to
prepare or to submit a certification
with an application or proposal under
these regulations, and the application
or proposal involves an
investigational new drug (within the
meaning of 21 U.S.C. 355(t) or
357(d)) or a significant risk device (as
defined in 21 CFR 812. 3(m)), the
institution shall identity the drug or
device in the certification. The
institution shall also state whether the
30-day interval required for
investigational new drugs by 21 CFR
312.1(a) and tor significant risk
devices by 21 CFR 812.30 has
elapsed, or whether the Food and
Drug Administration has waived that
requirement.
If the 30-day interval
has expired, the institution shall state
whether the Food and Drug
Administration has requested that the
sponsor continue to withhold or
restrict the use of the drug or device
m human subjects.
If the 30-day
interval has riot expired, and a waiver
has not been received, the institution
shall send a statement
to the
Department upon expiration of the
interval. The Department
will not
consider a certification acceptable
until the institution has submitted a
statement that the 30-day interval has
elapsed, and the Food and Drug
Administration
lias not requested
it to
limit the use of the drug or device, or
that the Food and Drug
Administration has waived the 30-day
interval.
§ 46.122
Use of Federal funds.
Federal funds administered by ihe
Department may not be expended for
research involving human subjects
unless the requirement of these
regulations, including
all subparts of
these regulations, have been satisfied.
§ 46,iI 23 Early termination of
research funding; evaluation or
subsequent applications and
proposals.
(a) The Secretary may require that
Department funding for any project
be terminated or suspended in the
manner prescribed in applicable
program requirements, when the
Secretary finds an institution has
rriateriailly failed to comply with the
terms of these regulations.
(b) In making decisions about
funding applications or proposals
covered by these regulations the
Secretary may take into account,
in
addition to all other eligibility
requirements and program criteria,
factors such as whether the applicant
has been subject to a termination or
suspension under paragraph (a) of this
section and whether the applicant or
the person who would direct the
scientific and technical aspects of an
activity has in the judgment of the
Secretary materially failed to
discharge responsibility for the
protection of the rights and welfare of
human subjects (whether or not
Depaitmcnt funds were involved).
§ 46.124 Conditions,
With respect to any research
project or any class of research
projects the Secretary may impose
additional conditions prior to or at the
time oi funding when in the
Secretary’s judgment additional
conditions arc necessary for the
protection of human subjects.
Subpart B— Additional Protections
Pertaining to Research
Development, and Related
Activities Involving Fetuses,
*
Pregnant Women, and Human in
Vitro Fertilization’
Soi'ma
40 ) R
135;g. Au*
8. |975. 41 FR
1758, January
II.
1978,
4.1 f-R
.51559, November 3,
|y7#
§ 46,201
Applicability.
(i\)
Yhe regulations
in
this subpan
are applicable to
all Department of
Health, Hdueation, and Welfare
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1 grams and contract supporting
research, development, and related
activities involving: (I) The fetus, (2)
pregnant women, and (3) human in
vitro
fertilization,
(b) Nothing
in this subpart shall be
construed as indicating that
compliance with the procedures set
forth herein will
in any way render
inapplicable pertinent State or local
laws bearing upon activities covered
by this subpart.
(c> The requirements of this
subpart are in addition to those
imposed under the other subpairts of
this part,
f 46,202
Purpose.
it
is the purpose of this subpan to
provide additional safeguards in
reviewing activities to which
this
subpart
is applicable to assure that
they conform
to appropriate ethical
standards and relate
to important
societal needs.
} 46.203
Definitions,
As used in
this subpart:
(a)
* ‘Secretary ” means the
Secretary of Health, Education, and
Welfare and any other officer or
employee of the Department of
Health, Education, and Welfare to
whom authority has been delegated.
(h) “Pregnancy ” encompasses the
period of time from confirmation of
implantation (through any of the
presumptive signs of pregnancy, such
as missed menses, or by a medically
acceptable pregnancy
test), until
expulsion or extraction of the fetus.
(c) “Fetus’* means (he product of
conception from the time of
implantation (as evidenced by any of
the presumptive signs of pregnancy,
such as missed menses, or a
medically acceptable pregnancy
test),
until
a determination
is made,
following explusion or extraction of
the fetus, that
it
is viable.
(d) “Viable” as
it pertains to the
IV uis means being able, after either
spontaneous or induced delivery,
to
survive (given the benefit of available
medical therapy) to the point of
independently maintaining heart
beat and respiration. The Secretary
may from
cirrte to rime, taking into
account medical advances, publish in
the Federal R lcister guidelines
to assist
in determining whether a
fetus
is vtable for purposes of this
subpan.
If a fetus
is viable after
delivery,
it
is a premature
infant,
(e) “Noriviable fetus” means a
fetus
e.x uirro which, although living,
is not viable.
(0 '‘Dead fetus” means a fetus ex
utero which exhibits neither
heartbeat, spontaneous respiratory
activity, spontaneous movement of
voluntary muscles, nor pulsation of
the umbilical cord
(if still attached).
(g)
“fii vitro fertilization” means
any
fertilization of human ova which
occurs outside the body of a female,
either through admixture of donor
human sperm and ova or by any other
means.
§ 46.204
Ethics! Advisory
Boards.
*
(a) One or more Ethical Advisory
Boards shall be established by the
Secretary. Members of these board(s)
shall be so selected that the feoard(s)
will be competent to deal with
medical,
legal, social, ethical, and
related issues and may indude,
for
example, research scientists,
physichins, psychologists,
sociologists, educators, lawyers, and
ethicists, as well as representatives of
the general public. No board member
may be a regular,
full time employee
of the Department of Health,
Education, and Welfare.
(b) At the request of the Secretary,
the Ethical Advisory Board shall
render advice consistent with the
policies and requirements of this Part
as to ethical issues, involving
activities covered by this sub part,
raised by individual applications or
proposals.
In addition, upon request
by the Secretary, the Board shall
render advice as to classes of
applications or proposals and general
policies, guidelines, and procedures.
(c) A Board may establish, with
the approval of the Secretary, classes
of applications or proposals which:
(I) Must be submitted to the Board,
or (2) need not be submitted to the
Board. Where the Board so
establishes a class of applications or
proposals which must be submitted,
no application or proposal within the
class may be funded by the
Department or any component thereof
until the application or proposal has
been reviewed by the Board and the
Board has rendered advice as to its
acceptability from an ethical
standpoint
(d) No application or proposal
involving human in vitro fertilization
may be funded by the Department or
any component thereof until the
application or proposal has been
reviewed by the Ethical Advisory
Board and the Board has rendered
advice as to
its acceptability from an
ethical standpoint.
8 46.205
Additional duties of f&t
instituting
Board* In
connection with activities
InvdvinR fetuses, pregnant
women, or human In vitro
fertilization.
(a) In addition to the
responsibilities prescribed for
Institutional Review Boards under
Subpart A of this part, the applicant 's
or offeror's Board shall, with respect
to activities covered by
ithis subpart,
carry out the following additional
duties:
(1) Determine that all aspects of
the activity meet the requirements of
this subpart;
(2) Determine that adequate
consideration has been given to the
manner in which potential subjects
will be selected, and adequate
provision has been made by the
applicant or offeror for monitoring
the actual informed consent process
(e g., through such mechanisms,
when appropriate, as participation by
the
Institutional Review Board or
subject advocates
in:
(i) Overseeing
the actual process by which
individual concerns required by
thii*
subpan arc secured either by
approving induction of each
individual into the activity or
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verifying, perhaps through sampling,
that approved procedures for
induction of individuals into the
activity are being followed, and
(ii)
monitoring the progress of the
activity and intervening as necessary
through such steps as visits to the
activity site and continuing evaluation
to determine
if any unanticipated
risks have arisen);
(3) Carry out such other
responsibilities as may be assigned by
the Secretary.
(b) No award may be issued until
the applicant or offeror has certified
to the Secretary that the Institutional
Review Board has made the
determinations required under
paragraph (a) of this section and the
Secretary has approved these
determinations, as provided in
§ 46. 120 of Subpan A of this pan.
(c) Applicants or offerors seeking
support for activities covered by this
subpart must provide for the
designation of ait Institutional Review
Board, subject to approval by the
Secretary, where no such Board has
been established under Subpart A of
rhis
part,
§ 46,206
General limitations.
<a) No activity to which this
subpart
is applicable may be
undertaken unless:
(
{
) Appropriate studies on animals
and nonpregnant individuals have
been completed;
(2) Except where the purpose of
the activity
is to meet the health
needs of the mother or the particular
Ictus,
the risk to the fetus
is minimal
and.
in
ail cases,
is the least possible
risk for achieving the objectives of
the
activity.
( 3 ) Individuals engaged
in the
activity will have no part
in:
(i) Any
decisions as to the timing, method,
ami procedures used to terminate the
pregnancy, and
(ii) determining the
viability of the fetus at the
termination of the pregnancy; and
( 4
) No procedural changes which
may cause greater than minimal
risk
to the fetus or the pregnant woman
Will he introduced into the procedure
for terminating the pregnancy solely
in the interest of the activity.
(b) No inducements, monetary or
otherwise, rnay be offered to
terminate pregnancy for purposes of
the activity.
(40 FR 33528. Aug
8.
JV75. as amended
at
40 FR 51638. Nov.
6,
1975)
| 46.2(17
Activities directed
toward pregnant women as
subjects.
(a) No pregnant woman may be
involved as a subject
in an activity
covered by
this subpart unless: (I)
The purpose of the activity
is to meet
the health needs of the mother and the
fetus will be placed at risk only to the
minimum extent necessary to meet
such needs, or (2) the risk to the fetus
is minimal.
(b) An activity permitted under
paragraph (at of this section may be
conducted only
if the mother and
father are legally competent and have
given their informed consent after
having been
fully informed regarding
possible impact on the fetus, except
that the father's informed consent
need not be secured
if: (1) The
purpose of the activity
is to meet the
health needs of the mother; (2) his
identity or whereabouts cannot
reasonably be ascertained;
(3) he
is
not reasonably available: or (4) the
pregnancy resulted from rape.
§ 46.20#
Activities directed
toward fetuses in utero as
subjects.
(a) No Ictus
in utero may be
involved as a subject
in any activity
covered by
this subpan unless:
(!)
The purpose of the activity
is
to meet
the health needs of she particular fetus
and the fetus will be placed at risk
only to the minimum extent necessary
to meet such needs, or (2) the risk to
the fetus imposed by the research
is
minimal and the purpose of the
activity
is the development of
important biomedical knowledge
which cannot be obtained by other
means.
(b) Art activity permitted under
paragraph (a) of this section rnay be
conducted only
if the mother and
father are legally competent and have
given their informed consent, except
that the father’s consent need not be
secured
if:
( j) His identity or
whereabouts cannot reasonably be
ascertained, (2) he
is not reasonably
available, or <3) the pregnancy
resulted from rape.
I 46.209
Activities directed
toward Musts ex utero,
including sionviable fetuses, as
subjects.
(a) Until
it has been ascertained
whether or not a fetus cx utero is
viable, a fetus cx utero may not be
involved as a subject in
art activity
covered by this subpart unless:
(1) There will be no added risk to
the fetus resulting from the activity,
and the purpose of the activity is the
development of important biomedical
knowledge which cannot be obtained
by other means, or
(2) The purpose of the activity is to
enhance the possibility of survival of
the particular fetus to the point of
viability.
(b) No non viable fetus may be
involved as a subject in an activity
covered by this subpart unless:
(1) Vitaf functions of the fetus w ill
not be artificially maintained,
(2) Experimental activities which
of themselves would terminate the
heartbeat or respiration of the fetus
will not be employed, and
(3) The purpose of the activity
is
the development of important
biomedical knowledge which cannot
be obtained by other means.
(e) In the event the fetus ex utero
is found to be viable,
it may be
included as a subject
in the activity
only to the extent permitted by and in
accordance with the requirements of
other subparts of this pan.
(d) An activity permitted under
paragraph fa) or (b) of this section
may be conducted only
if the mother
and lather arc legally competent and
have given their informed consent,
except that the father's informed
consent need not be secured
if: (I) his
identity or whereabouts cannot
reasonably be ascertained, (2) he
is
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not reasonably available, or (3) the
>pregn$ncy resulted from rape.
§ 46.210
Activities involving the
dead fetus, fetal material!, or the
placenta.
Activities involving the dead fetus,
mascerated feta! material, or cells,
tissue, or organs excised from a dead
fetus shall be conducted only in
accordance with any applicable State
or local laws regarding such
activities.
fi 46,211
Modification or waiver
of specific requirements.
Upon the request of an applicant or
offeror (with the approval of its
Institutional Review Board), the
Secretary may modify or waive
specific requirements of thus subpan,
with the approval of the Ethical
Advisory Board after such
opportunity tor public comment as
the Ethical Advisory Board considers
appropriate
in the particular instance.
In making such decisions, the
Secretary will consider whether the
risks to the subject are so outweighed
by the sum of the benefit to the
subject and the importance of the
knowledge
to be gained as to warrant
sudi modification or waiver and that
such benefits cannot be gained except
through a modification or waiver.
Any such modifications or waivers
wiil be published as notices
in
the
: MM KA( R EG I.ST I- K
Subpart C—- Additional Protect ions
Pertaining to Biomedical and
Behavioral Research Involving
FVisoners as Subjects
Source: 43 FR 53655, Nov
16.
1 97
K
§ 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, Education, and Welfare
involving prisoners as subjects.
(hi Nothing in this subpart shall be
comm rued as indicating that
compliance with the procedures
set
lorth herein will authorize research
involving prisoners as subjects, to the
cAtent such research
is limited or
barred by applicable State or local
law.
(c) The requirements of this
subpart arc
in addition to those
imposed under the other subparts of
this pan,
§ 46.302
Purpose,
Inasmuch as prisoners may be
under constraints because of their
incarceration which 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.
§ 46,303
Definitions.
As used
in
this subpart:
(a) “Secretary” means the
Secretary of Health, Education, and
Welfare and any other officer or
employee of the Department of
Health, Education, and Welfare to
whom authority has been delegated.
(b) “DHEW
means the
Department of Health, Education,
and Welfare.
(c)
11 Prisoner” means any
r individual involuntarily confined of
detained
in a penal institution. The
Itrm
is Intended to encompass
'
individuals scntenced'to such an
institution under a criminal or civil
statute, individuals^detained in other
facilities by virtue of statutes or
pmmitme*ii,procedures which
provide aftemativei to .aim iml
prosecution or incarceration in a
penal institution, |uxd .individuals
detained pending arraignment, trial,
or sentencing.
(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 .subpan, shall also
meet die following specific
requirements;
(a) A majority of the Board
of
Jf prisoner'members) sihatf
have no association with the prison(s^
involved, apart from theit|A
membership bn the Board?
l*§'
(b) At least one member of the*
Board,shall bew
a Prisoner, or^
pnsoaer. 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.
§ 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
lood, amenities and opportunity for
earnings in the prison, are. not of such
a magnitude that bis 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
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