[Federal Register Volume 66, Number 11 (Wednesday, January 17, 2001)]
[Rules and Regulations]
[Pages 3878-3883]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-1122]


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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: 
[email protected].

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