[Federal Register: January 17, 2001 (Volume 66, Number 11)]
[Rules and Regulations]
[Page 3878-3883]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17ja01-5]
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DEPARTMENT OF HEALTH AND HUMAN SERVICE
45 CFR Part 46
RIN 0925-AA14
Protection of Human Research Subjects
AGENCY: Department of Health and Human Services (DHHS).
ACTION: Final rule.
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SUMMARY: The Department of Health and Human Services (DHHS) is amending
its human subjects protection regulations. These regulations provide
additional protections for pregnant women and human fetuses involved in
research and pertains to human in vitro fertilization. The rule
continues the special protections for pregnant women and human fetuses
that have existed since 1975. The rule enhances the opportunity for
participation of pregnant women in research by promoting a policy of
presumed inclusion, by permitting the pregnant woman to be the sole
decision maker with regard to her participation in research, and by
exempting from the regulations six categories of research. The rule
also provides a mechanism for the Secretary of HHS to conduct or fund
research not otherwise approvable after consultation with an expert
panel and public review and comment.
DATES: Effective date: March 19, 2001.
FOR FURTHER INFORMATION CONTACT: Susan Sherman, JD, Office for Human
Research Protections (OHRP), 6100 Executive Blvd, Suite 3B01,
Rockville, MD 20892-7507. Telephone 301-496-7005. Email:
ShermanS@od.nih.gov.
SUPPLEMENTARY INFORMATION:
Background
The Department of Health and Human Services (DHHS) regulates
research involving human subjects conducted or supported by the agency
through regulations codified at Title 45, part 46, of the Code of
Federal Regulations. Subpart B of 45 CFR part 46, promulgated on August
8, 1975, pertains to research involving fetuses, pregnant women, and
human in vitro fertilization. The 1975 regulations were jointly
published in the Federal Register with the report and recommendations
of the National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research, Research on the Fetus (40 FR
33526). Subsequent changes were incorporated January 11, 1978 (43 FR
1758), November 3, 1978 (43 FR 51559), and June 1, 1994 (59 FR
[[Page 3879]]
28276). This preamble refers to these rules as the ``1975
regulations.''
Recent guidelines issued by components of DHHS have addressed the
participation of women in research as follows:
Food and Drug Administration 1993 Guideline for the Study
and Evaluation of Gender Differences in the Clinical Evaluation of
Drugs (58 FR 39406);
National Institutes of Health 1994 Guidelines on the
Inclusion of Women and Minorities as Subjects in Clinical Research (59
FR 14508); and
Centers for Disease Control and Prevention 1995 Policy on
the Inclusion of Women and Racial and Ethnic Minorities in Externally
Awarded Research (60 FR 47947), and February 16, 1996 policy Inclusion
of Women and Racial and Ethnic Minorities in Research.
These policies are all designed, in part, to improve the
opportunity for women to be included as subjects in research.
A Committee on the Ethical and Legal Issues Relating to the
Inclusion of Women in Clinical Studies of the Institute of Medicine
issued a report in 1994 on Women and Health Research that included the
recommendation that DHHS revise subpart B in accordance with the
Committee's other recommendations. The Committee believed that women
and men should have the opportunity to participate equally in the
benefits and burdens of research, and many of the Committee's
recommendations were aimed at enhancing the participation of women,
including pregnant women, in clinical research.
The National Task Force on AIDS Drug Development and the
Presidential Advisory Council on HIV/AIDS subsequently recommended that
the lack of paternal consent should not disqualify a pregnant woman
from participation in a federally funded clinical trial.
These guidelines and recommendations, and the lack of a formal
review of subpart B for over two decades, led DHHS to determine that a
substantive examination of subpart B was appropriate.
Based on this review the Department proposed to amend subpart B in
a Notice of Proposed Rulemaking (NPRM) published on May 20, 1998 (63 FR
27794). The Department proposed that a policy of presumed opportunity
for inclusion of pregnant women in research replace one of presumed
exclusion. The Department also concurred with the recommendations of
the National Task Force on AIDS Drug Development, the Presidential
Advisory Council on HIV/AIDS, and the IOM Committee regarding paternal
consent and proposed to modify the consent requirement to remove
potential barriers to research that might provide a medical benefit to
a fetus.
The exemptions in 45 CFR part 46, Subpart A, Basic DHHS Policy for
Protection of Human Research Subjects, were proposed to apply to
subpart B. These exemptions of certain categories of research (e.g.,
survey research without subject identifiers) have applied since 1981 to
research involving nonpregnant women.
In light of the 1993 legislative nullification of the regulatory
requirement for ethical advisory board review of research involving in
vitro fertilization of human ova (Public Law 103-43), the Department
proposed a mechanism for the Secretary to modify or waive certain
requirements of Subpart B, following consultation with experts and
public input, in place of the provision that the Department have a
standing ethical advisory board. Nonsubstantive technical, formatting,
and clarifying changes were also proposed.
Discussion of Comments
During the public comment period that ended August 18, 1998, the
Department received 13 public comments on the proposed rule from
interested parties. The comments are summarized as follows:
General Comments
One commenter endorsed the NPRM in its entirety. One commenter
suggested that there be three classes of research that mirror the
categories in subpart D of part 46, Additional DHHS Protections for
Children Involved as Subjects in Research. Those categories are: no
greater than minimal risk, greater than minimal risk but presenting the
prospect of direct benefit, and greater than minimal risk and no
prospect of direct benefit. The Department finds that modification of
the format of subpart B to parallel the categories of research in
subpart D would not enhance the protection of women or fetuses and
would likely cause confusion. Subpart B, since its inception in 1975
and in this final rule, requires that the risk to the fetus be the
least possible risk for achieving the research objectives and any risk
which is greater than minimal must hold out the prospect of direct
benefit for the fetus or the woman.
One commenter objected to distinctions between ``therapeutic'' and
``nontherapeutic'' research as illogical, because, by definition, the
purpose of research is always to contribute to generalizable knowledge.
The commenter noted that this distinction confuses therapy with
research. The Department concurs with this comment and has modified the
final rule to eliminate language implying that the purpose of research
is ever therapeutic. The final rule uses the phrases ``* * *
interventions or procedures that hold out the prospect of direct
benefit * * *'' and ``* * * research [that] holds out the prospect of
enhancing the probability of survival * * *'' to describe research from
which a subject may benefit (Sec. 46.204(b) and Sec. 46.205(b)(1)(i)).
Applicability (Section 46.201)
The Department proposed that the exemptions at 45 CFR 46.101(b)(1)-
(6) of subpart A apply to subpart B. These exemptions of six categories
of research were promulgated in 1981, subsequent to the last
substantive revision of subpart B, and have applied to research with
nonpregnant subjects since that time. Two commenters endorsed the
incorporation of the exemptions into subpart B. One commenter noted
that pregnancy should not preclude women from participating in these
types of research; one stated that pregnant women are autonomous
decision makers and should not be treated as vulnerable or impaired
because of their condition. Consistent with these comments, the
exemptions are retained in the final rule (Sec. 46.201(b)).
The Department has retained in the final rule language specifying
that the requirements of subpart B are in addition to those imposed
under the other subparts of 45 CFR part 46, for purposes of clarity
(Sec. 46.201(d)).
Definitions (Section 46.202)
The proposed definitions were substantively the same as those in
the 1975 regulations.
The Department proposed the following simplified definition of
``fetus:'' ``fetus means the product of conception during pregnancy
until a determination is made after delivery that it is viable.'' One
commenter noted that ``product of conception'' is generally understood
to mean the associated placenta as well. The Department intends that
research with the placenta prior to delivery be governed by 45 CFR
46.204, Research involving pregnant women or fetuses prior to delivery.
For purposes of clarity, the definition of ``fetus'' in the final rule
utilizes the phrase ``from implantation,'' which is the same phrase
used in the definition of ``pregnancy.''
Since 1975, subpart B has included the fetus ex utero until such
time as
[[Page 3880]]
viability of the fetus is determined. The Department proposed to
replace the phrase ``ex utero'' with ``after delivery.'' No comments
were received on that proposal and the final rule retains the proposed
language.
The Department also proposed the term ``newborn,'' equating newborn
with ``fetus after delivery,'' because some persons may prefer one term
to the other depending on the length of the gestation period. Two
commenters found the introduction of this term confusing and
inconsistent because after delivery there exists an entity that could
be called either fetus or newborn. The Department concurs with these
comments and has deleted the term ``newborn'' from the final rule.
One commenter noted that newborns can be of any species and
believed that the term ``child'' should be used in place of
``newborn.'' Another commenter stated that a viable fetus is generally
understood to mean a fetus after the point of viability, generally at
5-6 months gestation. In response to these comments the Department has
defined ``viable'' in the final rule and emphasized that, as it
pertains to the fetus, ``viable'' means a fetus after delivery and the
regulations at 45 CFR part 46, subpart D, are applicable
(Sec. 46.202(h)).
Research Involving Pregnant Women or Fetuses Prior to Delivery (Section
46.204)
For purposes of clarity, the scope of Sec. 46.204 has been narrowed
in the final rule to research involving pregnant women or fetuses prior
to delivery, and those provisions of proposed Sec. 46.204 that are
applicable to research involving fetuses after delivery have been
repeated in section Sec. 46.205 (see Sec. 46.205(a)(1)-(6) and
(b)(1)(i)).
The Department proposed to require, as a prerequisite to research
on pregnant women or fetuses, preclinical and clinical studies,
including studies on nonpregnant women, that provide data for assessing
potential risks to pregnant women and fetuses. One commenter endorsed
the increased specificity and noted that it would ensure that
reproductive toxicity data are available. Another commenter found that
to require pregnant women to wait until studies have been conducted on
nonpregnant women is to neglect them as a population. The Department
notes that preclinical and clinical studies are required only when
scientifically appropriate. The final rule retains the proposed
provision for preclinical and clinical studies (Sec. 46.204(a) and
Sec. 46.205(a)(1)).
To strengthen protections for the pregnant woman and fetus, the
Department proposed a new informed consent provision: that the woman be
fully informed regarding the reasonably foreseeable impact of the
research on the fetus. No commenters objected to this provision. The
final rule, at Sec. 46.204(e), retains this requirement with the
clarification that it also applies to the legally authorized
representative. This provision is repeated in Sec. 46.205(a)(2), so
that the person whose informed consent is a prerequisite to
participation in the research must be fully informed of the reasonably
foreseeable impact of the research on the fetus.
One commenter stated that informed consent should highlight known
or suspected risks and should incorporate unknown harms. The Department
notes that provisions of subpart A at 45 CFR part 46.116(a)(2) and
Sec. 46.116(b)(1), respectively, also applicable to subpart B, address
these concerns. The commenter further noted that researchers should
work to ensure that the woman or her legally authorized representative
understands the information that has been disclosed, that checks for
understanding should be tailored according to the situation of
particular women or representatives, and women should be encouraged to
discuss research participation with their obstetrician before making a
final decision about enrollment. The Department notes that ensuring
that information is understood and checks for understanding tailored to
particular situations are not precluded by the regulations, nor are
they unique to research with pregnant women. Subpart A affords IRBs the
opportunity and the authority to ensure the adequacy of informed
consent and protections by imposing additional requirements or
monitoring the research or the consent process. Similarly, with regard
to the suggestion concerning encouragement of discussion with an
obstetrician, the Department notes that the rules do not preclude
encouragement to discuss participation with obstetricians or any other
individuals and that subpart A requires that consent be sought only
under circumstances that provide sufficient opportunity to consider
participation (45 CFR 46.116).
The Department proposed to modify the consent requirements in the
1975 regulations by permitting research with pregnant women or fetuses
prior to delivery based on the consent of the woman or her legally
authorized representative. The Department recognizes and encourages
paternal involvement in decisions affecting the pregnant woman and
fetus prior to delivery. Nonetheless, in some cases the father's
consent has been a barrier to participation in research of the woman or
fetus prior to delivery. The recommendations of the National Task Force
on AIDS Drug Development, the Presidential Advisory Council on HIV/
AIDS, and the IOM Committee were unanimous that the consent of the
father should not be a condition of the participation of a pregnant
woman in research.
Ten commenters endorsed or applauded the proposal to modify the
parental consent requirement, many describing specific research trials
in which pregnant women were unable to participate in potentially
beneficial research because of the requirement that the father's
consent be secured. One commenter believed the consent of the father
should continue to be required and that waivers from the Secretary
should be sought if the father's consent is difficult to obtain. The
Department concludes that the decision making authority for research
participation of the pregnant woman or fetus prior to delivery should
rest with the pregnant woman and has retained this provision in the
final rule (Sec. 46.204(d)).
One commenter indicated that the rules are unclear whether a
researcher may inform a pregnant woman of nonresearch alternatives. The
Department notes that subpart B does not address alternatives to
research, but that subpart A, at 45 CFR part 46.116(a)(4), also
applicable to subpart B, requires disclosure of appropriate alternative
procedures or courses of treatment that might be advantageous to the
subject.
The Department has also decided to continue the use of the word
``terminate'' in sections 204 and 205 instead of utilizing the proposed
change to the word ``abort.'' The Department believes that the original
language is clearer.
Research Involving Fetuses After Delivery (Section 46.205)
As indicated above, those provisions proposed in Sec. 46.204 that
are applicable to research involving fetuses after delivery are
reiterated in the final rule under Sec. 46.205(a) and (b)(1)(i).
One commenter requested that the Department explain why this
section is separate from subpart D. As noted above, the 1975
regulations extended the definition of fetus to include the fetus ex
utero until such time as a fetus is determined to be viable. The final
rule continues this extension because nonviable fetuses, and fetuses
whose viability has not yet been determined
[[Page 3881]]
after delivery, require protection and are not covered by subpart D.
Accordingly, subpart B permits research with fetuses of uncertain
viability only if the research holds out the prospect of enhancing the
probability of survival or there will be no risk resulting from the
research and the purpose is the development of important biomedical
knowledge that cannot be obtained by other means (Sec. 46.205(b)).
Research with nonviable fetuses after delivery, which must be
considered dying subjects, must meet the five criteria at
Sec. 46.205(c)(1)-(5), also intended to provide protection for such
subjects.
Section 498(a), ``Fetal Research,'' of the Public Health Service
Act, 42 U.S.C. 289g(a), places statutory restrictions on research
involving nonviable living fetuses ex utero or living fetuses ex utero
for whom viability has not been ascertained. The statute permits
research under either of the following two conditions: ``the research *
* * (1) may enhance the well-being or meet the health needs of the
fetus or enhance the probability of its survival to viability; or (2)
will pose no added risk of suffering, injury, or death to the fetus and
the purpose * * * is the development of important biomedical knowledge
that cannot be obtained by other means.'' This rule exceeds those
requirements for fetuses of uncertain viability by permitting research
only if it either (1) holds out the prospect of enhancing the
probability of survival of the particular fetus to the point of
viability, or (2) poses no risk to the fetus and the purpose is the
development of important biological knowledge that cannot be obtained
by other means. This rule also exceeds the statutory requirements for
nonviable living fetuses ex utero by specifying that vital functions of
the nonviable fetus may not be artificially maintained and the research
may not terminate the heartbeat or respiration of the fetus.
The consent requirements for research involving fetuses of
uncertain viability and nonviable fetuses at Sec. 46.205(b)(2) and
Sec. 46.205(c)(5), respectively, also ensure protection of the fetus.
Research involving fetuses of uncertain viability may proceed with the
consent of either parent (or under certain circumstances the consent of
a legally authorized representative), but the research must hold the
prospect of enhancing the probability of survival of the fetus to the
point of viability or pose no risk to the fetus. The Department
recognizes that, in cases of uncertain viability, a decision regarding
research participation must often be made very quickly, especially
where the research presents the prospect of enhancing the probability
of survival of the fetus. Thus, the consent of only one parent (or
legally authorized representative) is required. However, if both
parents are readily available at the time when a decision is needed,
reasonable efforts should be made to provide all relevant information
to both parents. The Department believes that research involving the
nonviable fetus should only proceed with the consent of both parents
(unless one is unavailable, incompetent, or temporarily incapacitated),
and the consent of a representative is expressly prohibited. The
individual(s) providing consent under Sec. 46.205(b)(2) or (c)(5) must
be fully informed regarding the reasonably foreseeable impact of the
research on the fetus (Sec. 46.205(a)(2)).
Research after delivery, involving fetuses determined to be viable,
is governed by Subpart D (Sec. 46.205(d)).
Research Not Otherwise Approvable That Presents Certain Opportunities
section 46.207)
The Department proposed to replace the 1975 regulatory authority of
the Secretary to modify or waive specific requirements with the
approval of an ethical advisory board, with the authority to modify or
waive requirements after consultation with appropriate experts and
opportunity for public review and comment. The proposal would have
required the Secretary to consider whether the risks to the subjects
were so outweighed by the sum of the benefits to the subjects and the
importance of the knowledge to be gained as to warrant modification or
waiver. One commenter noted that the proposed waiver provision did not
require IRB review, as does the similar section in subpart D (45 CFR
46.407). The commenter further noted that the proposed wording appeared
to require that the overarching consideration be ``beneficence'' based,
and that adopting the language in 45 CFR 46.407 would encompass all of
the ethical principles in the Belmont Report and ensure consistency
between subparts B and D. The Department concurs with these comments
and the final rule, at Sec. 46.207, is consistent with 45 CFR 46.407,
with conforming and clarifying changes.
Under this provision the waiver authority is limited to the
requirements of Sec. 46.204 applicable to pregnant women and fetuses
prior to delivery. The other requirements of subpart B, including those
in Sec. 46.205, cannot be waived. Even though the Secretary has the
authority to waive the requirements of Sec. 46.205 that exceed the
statutory requirements of section 498(a), ``Fetal Research,'' of the
Public Health Service Act, 42 U.S.C. 289g(a) (see discussion of
Sec. 46.205 above), it was determined that the additional protections
afforded by Sec. 46.205 are essential and should not be waived under
any circumstances.
Conclusion
After considering the comments, the Department is adopting the rule
as proposed except for the changes noted above and editorial changes to
clarify the intent of the regulation. Distinctions between therapeutic
and nontherapeutic research are eliminated. The term ``newborn'' is
deleted in the final rule for purposes of clarity, and the definition
of ``viable'' as it pertains to the fetus is clarified. Section 46.207,
regarding approval by the Secretary of research that would not
otherwise be approvable under Sec. 46.204, is modified consistent with
the similar provision in subpart D. The Department has also
incorporated additional nonsubstantive editorial and clarifying
revisions in the final rule.
The rule is effective 60 days after publication to give
Institutional Review Boards (IRBs) time to incorporate the regulations
into their review of research protocols. All initial and ongoing
projects reviewed after the effective date by IRBs under Multiple
Project Assurances or other Assurances with the DHHS, Office for Human
Research Protections, OHRP (formerly OPRR), must be reviewed in
accordance with these rules.
Executive Order 12866
Executive Order 12866 requires that all regulatory actions reflect
consideration of the costs and benefits they generate and that they
meet certain standards, such as avoiding the imposition of unnecessary
burdens on the affected public. If an action is deemed to fall within
the scope of the definition of the term ``significant regulatory
action'' contained in Sec. 3(f) of the Order, a pre-publication review
by the Office of Management and Budget's (OMB's) Office of Information
and Regulatory Affairs (OIRA) is necessary. OMB deemed this rule a
``significant regulatory action,'' as defined by Executive Order 12866.
Therefore, the rule was submitted to OIRA for review prior to its
publication in the Federal Register.
Regulatory Flexibility Act
The Regulatory Flexibility Act (5 U.S.C. Chapter 6) requires that
regulatory actions be analyzed to determine whether they create a
significant impact on a substantial number of small entities. This rule
primarily affects individual research
[[Page 3882]]
subjects and institutions that receive funding from the Department of
Health and Human Services for research involving human subjects. It
will not have the effect of imposing significant additional costs on
small research institutions that are within the definition of small
entities. Therefore, the Secretary certifies that this rule will not
have significant impact on a substantial number of small entities and
that preparation of an initial regulatory flexibility analysis is not
required.
Paperwork Reduction Act
This rule does not contain any new information collection
requirements that are subject to Office of Management and Budget (OMB)
approval under the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter
35).
List of Subjects in 45 CFR Part 46
Health--clinical research, medical research.
Dated: September 21, 2000.
David Satcher,
Assistant Secretary for Health and Surgeon General.
Approved: October 30, 2000.
Donna E. Shalala,
Secretary of Health and Human Services.
Accordingly, the Department of Health and Human Services amends
part 46 of the Regulations for the Protection of Human Subjects (45 CFR
part 46), as follows:
1. authority citation for 45 CFR part 46 is revised to read as
follows:
Authority: 5 U.S.C. 301; 42 U.S.C. 289(a).
2. Supbart B of 45 CFR part 46 is revised to read as follows:
Subpart B--Additional Protections for Pregnant Women and Human
Fetuses Involved in Research, and Pertaining to Human In Vitro
Fertilization
Sec.
46.201 To what do these regulations apply?
46.202 Definitions.
46.203 Duties of IRBs in connection with research involving
pregnant women, fetuses, and human in vitro fertilization.
46.204 Research involving pregnant women or fetuses prior to
delivery.
46.205 Research involving fetuses after delivery.
46.206 Research involving, after delivery, the placenta, the dead
fetus, or fetal material.
46.207 Research not otherwise approvable which presents an
opportunity to understand, prevent, or alleviate a serious problem
affecting the health or welfare of pregnant women or fetuses.
Sec. 46.201 To what do these regulations apply?
(a) Except as provided in paragraph (b) of this section, this
subpart applies to all research involving pregnant women or human
fetuses, and to all research involving the in vitro fertilization of
human ova, conducted or supported by the Department of Health and Human
Services (DHHS). This includes all research conducted in DHHS
facilities by any person and all research conducted in any facility by
DHHS employees.
(b) The exemptions at Sec. 46.101(b)(1) through (6) are applicable
to this subpart.
(c) The provisions of Sec. 46.101(c) through (i) are applicable to
this subpart. Reference to State or local laws in this subpart and in
Sec. 46.101(f) is intended to include the laws of federally recognized
American Indian and Alaska Native Tribal Governments.
(d) The requirements of this subpart are in addition to those
imposed under the other subparts of this part.
Sec. 46.202 Definitions.
The definitions in Sec. 46.102 shall be applicable to this subpart
as well. In addition, as used in this subpart:
(a) Dead fetus means a fetus after delivery that exhibits neither
heartbeat, spontaneous respiratory activity, spontaneous movement of
voluntary muscles, nor pulsation of the umbilical cord. Delivery means
complete separation of the fetus from the woman by expulsion or
extraction or any other means.
(b) Fetus means the product of conception from implantation until a
determination is made after delivery that it is viable.
(c) In 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.
(d) Nonviable fetus means a fetus after delivery that, although
living, is not viable.
(e) Pregnancy encompasses the period of time from implantation
until delivery. A woman shall be assumed to be pregnant if she exhibits
any of the pertinent presumptive signs of pregnancy, such as missed
menses, until the results of a pregnancy test are negative or until
delivery.
(f) 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.
(g) Viable as it pertains to the fetus means being able, after
delivery, to survive (given the benefit of available medical therapy)
to the point of independently maintaining heartbeat and respiration.
The Secretary may from time to time, taking into account medical
advances, publish in the Federal Register guidelines to assist in
determining whether a fetus is viable for purposes of this subpart. If
a fetus after delivery is viable then it is a child as defined by
Sec. 46.402(a), and subpart D of this part is applicable.
Sec. 46.203 Duties of IRBs in connection with research involving
pregnant women, fetuses, and human in vitro fertilization.
In addition to other responsibilities assigned to IRBs under this
part, each IRB shall review research covered by this subpart and
approve only research which satisfies the conditions of all applicable
sections of this subpart and the other subparts of this part.
Sec. 46.204 Research involving pregnant women or fetuses prior to
delivery.
Pregnant women or fetuses prior to delivery may be involved in
research if all of the following conditions are met:
(a) Where scientifically appropriate, preclinical studies,
including studies on pregnant animals, and clinical studies, including
studies on nonpregnant women, have been conducted and provide data for
assessing potential risks to pregnant women and fetuses;
(b) The risk to the fetus is not greater than minimal, or any risk
to the fetus which is greater than minimal is caused solely by
interventions or procedures that hold out the prospect of direct
benefit for the woman or the fetus;
(c) Any risk is the least possible for achieving the objectives of
the research;
(d) The woman's consent or the consent of her legally authorized
representative is obtained in accord with the informed consent
provisions of subpart A of this part, unless altered or waived in
accord with Sec. 46.101(i) or Sec. 46.116(c) or (d);
(e) The woman or her legally authorized representative, as
appropriate, is fully informed regarding the reasonably foreseeable
impact of the research on the fetus or resultant child;
(f) For children as defined in 45 CFR 46.402(a) who are pregnant,
assent and permission are obtained in accord with the provisions of
subpart D of this part;
(g) No inducements, monetary or otherwise, will be offered to
terminate a pregnancy;
(h) Individuals engaged in the research will have no part in any
decisions as to the timing, method, or procedures used to terminate a
pregnancy; and
[[Page 3883]]
(i) Individuals engaged in the research will have no part in
determining the viability of a fetus.
Sec. 46.205 Research involving fetuses after delivery.
(a) After delivery, fetuses may be involved in research if all of
the following conditions are met:
(1) Where scientifically appropriate, preclinical and clinical
studies have been conducted and provide data for assessing potential
risks to fetuses.
(2) The individual(s) providing consent under paragraph (b)(2) or
(c)(5) of this section is fully informed regarding the reasonably
foreseeable impact of the research on the fetus or resultant child.
(3) No inducements, monetary or otherwise, will be offered to
terminate a pregnancy.
(4) Individuals engaged in the research will have no part in any
decisions as to the timing, method, or procedures used to terminate a
pregnancy.
(5) Individuals engaged in the research will have no part in
determining the viability of a fetus.
(6) The requirements of paragraph (b) or (c) of this section have
been met as applicable.
(b) Fetuses of uncertain viability. After delivery, and until it
has been ascertained whether or not a fetus is viable, a fetus may not
be involved in research covered by this subpart unless the following
additional conditions are met:
(1) The IRB determines that:
(i) The research holds out the prospect of enhancing the
probability of survival of the particular fetus to the point of
viability, and any risk is the least possible for achieving the
objectives of the research, or
(ii) The purpose of the research is the development of important
biomedical knowledge which cannot be obtained by other means and there
will be no risk to the fetus resulting from the research; and
(2) The legally effective informed consent of either parent of the
fetus or, if neither parent is able to consent because of
unavailability, incompetence, or temporary incapacity, the legally
effective informed consent of either parent's legally authorized
representative is obtained in accord with subpart A of this part,
unless altered or waived in accord with Sec. 46.101(i) or
Sec. 46.116(c) or (d).
(c) Nonviable fetuses. After delivery, a nonviable fetus may not be
involved in research covered by this subpart unless all of the
following additional conditions are met:
(1) Vital functions of the fetus will not be artificially
maintained;
(2) The research will not terminate the heartbeat or respiration of
the fetus;
(3) There will be no risk to the fetus resulting from the research;
(4) The purpose of the research is the development of important
biomedical knowledge that cannot be obtained by other means; and
(5) The legally effective informed consent of both parents of the
fetus is obtained in accord with subpart A of this part, except that
the waiver and alteration provisions of Sec. 46.116(c) and (d) do not
apply. However, if either parent is unable to consent because of
unavailability, incompetence, or temporary incapacity, the informed
consent of one parent of a nonviable fetus will suffice to meet the
requirements of this paragraph. The consent of a legally authorized
representative of either or both of the parents of a nonviable fetus
will not suffice to meet the requirements of this paragraph.
(d) Viable fetuses. A fetus, after delivery, that has been
determined to be viable is a child as defined by Sec. 46.402(a) and may
be included in research only to the extent permitted by and in accord
with the requirements of subparts A and D of this part.
Sec. 46.206 Research involving, after delivery, the placenta, the dead
fetus, or fetal material.
(a) Research involving, after delivery, the placenta; the dead
fetus; macerated fetal material; or cells, tissue, or organs excised
from a dead fetus, shall be conducted only in accord with any
applicable Federal, State, or local laws and regulations regarding such
activities.
(b) If information associated with material described in paragraph
(a) of this section is recorded for research purposes in a manner that
living individuals can be identified, directly or through identifiers
linked to those individuals, those individuals are research subjects
and all pertinent subparts of this part are applicable.
Sec. 46.207 Research not otherwise approvable which presents an
opportunity to understand, prevent, or alleviate a serious problem
affecting the health or welfare of pregnant women or fetuses.
The Secretary will conduct or fund research that the IRB does not
believe meets the requirements of Sec. 46.204 only if:
(a) The IRB finds that the research presents a reasonable
opportunity to further the understanding, prevention, or alleviation of
a serious problem affecting the health or welfare of pregnant women or
fetuses; and
(b) The Secretary, after consultation with a panel of experts in
pertinent disciplines (for example: science, medicine, ethics, law) and
following opportunity for public review and comment, including a public
meeting announced in the Federal Register, has determined either:
(1) That the research in fact satisfies the conditions of
Sec. 46.204, as applicable, or
(2) The following:
(i) The research presents a reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of pregnant women or fetuses;
(ii) The research will be conducted in accord with sound ethical
principles; and
(iii) Informed consent will be obtained in accord with the informed
consent provisions of subpart A and other applicable subparts of this
part, unless altered or waived in accord with Sec. 46.101(i) or
Sec. 46.116(c) or (d).
[FR Doc. 01-1122 Filed 1-16-01; 8:45 am]
BILLING CODE 4140-01-P