[Federal Register Volume 74, Number 128 (Tuesday, July 7, 2009)]
[Notices]
[Pages 32170-32175]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-15954]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institutes of Health Guidelines for Human Stem Cell
Research
SUMMARY: The National Institutes of Health (NIH) is hereby publishing
final ``National Institutes of Health Guidelines for Human Stem Cell
Research'' (Guidelines).
On March 9, 2009, President Barack H. Obama issued Executive Order
13505: Removing Barriers to Responsible Scientific Research Involving
Human Stem Cells. The Executive Order states that the Secretary of
Health and Human Services, through the Director of NIH, may support and
conduct responsible, scientifically worthy human stem cell research,
including human embryonic stem cell (hESC) research, to the extent
permitted by law.
These Guidelines implement Executive Order 13505, as it pertains to
extramural NIH-funded stem cell research, establish policy and
procedures under which the NIH will fund such research, and helps
ensure that NIH-funded research in this area is ethically responsible,
scientifically worthy, and conducted in accordance with applicable law.
Internal NIH policies and procedures, consistent with Executive Order
13505 and these Guidelines, will govern the conduct of intramural NIH
stem cell research.
DATES: Effective Date: These Guidelines are effective on July 7, 2009.
Summary of Public Comments on Draft Guidelines: On April 23, 2009
the NIH published draft Guidelines for research involving hESCs in the
Federal Register for public comment, 74 FR 18578 (April 23, 2009). The
comment period ended on May 26, 2009.
The NIH received approximately 49,000 comments from patient
advocacy groups, scientists and scientific societies, academic
institutions, medical organizations, religious organizations, and
private citizens. The NIH also received comments from members of
Congress. This Notice presents the final Guidelines together with the
NIH response to public comments that addressed provisions of the
Guidelines.
Title of the Guidelines, Terminology, and Background
Respondents felt the title of the NIH draft guidelines was
misleading, in that it is entitled ``National Institutes of Health
Guidelines for Human Stem Cell Research,'' yet addresses only one type
of human stem cell. The NIH notes that although the Guidelines pertain
primarily to the donation of embryos for the derivation of hESCs, one
Section also applies to certain uses of both hESCs and human induced
pluripotent stem cells. Also, the Guidelines discuss applicable
regulatory standards when research involving human adult stem cells or
induced pluripotent stem cells constitutes human subject research.
[[Page 32171]]
Therefore, the title of the Guidelines was not changed.
Respondents also disagreed with the definition of human embryonic
stem cells in the draft Guidelines, and asked that the NIH define them
as originating from the inner cell mass of the blastocyst. The NIH
modified the definition to say that human embryonic stem cells ``are
cells that are derived from the inner cell mass of blastocyst stage
human embryos, are capable of dividing without differentiating for a
prolonged period in culture, and are known to develop into cells and
tissues of the three primary germ layers.''
Financial Gain
Respondents expressed concern that derivers of stem cells might
profit from the development of hESCs. Others noted that because the
stem cells eligible for use in research using NIH funding under the
draft Guidelines are those cells that are subject to existing patents,
there will be insufficient competition in the licensing of such rights.
These respondents suggested that this could inhibit research, as well
as increase the cost of any future clinical benefits. The Guidelines do
not address the distribution of stem cell research material. It is,
however, the NIH's expectation that stem cell research materials
developed with NIH funds, as well as associated intellectual property
and data, will be distributed in accordance with the NIH's existing
policies and guidance, including ``Sharing Biomedical Research
Resources, Principles and Guidelines for Recipients of NIH Grants and
Contracts'' and ``Best Practices for the Licensing of Genomic
Inventions.'' http://ott.od.nih.gov/policy/Reports.html Even where such
policies are not directly applicable, the NIH encourages others to
refrain from imposing on the transfer of research tools, such as stem
cells, any conditions that hinder further biomedical research. In
addition, the Guidelines were revised to state that there should be
documentation that ``no payments, cash or in kind, were offered for the
donated embryos.''
Respondents were concerned that donor(s) be clearly ``apprised up
front by any researchers that financial gain may come from the donation
and that the donor(s) should know up front if he/she will share in the
financial gain.'' The Guidelines address this concern by asking that
donor(s) was/were informed during the consent process that the donation
was made without any restriction or direction regarding the
individual(s) who may receive medical benefit from the use of the stem
cells, such as who may be the recipients of cell transplants. The
Guidelines also require that the donor(s) receive(s) information that
the research was not intended to provide direct medical benefit to the
donor(s); that the results of research using the hESCs may have
commercial potential, and that the donor(s) would not receive financial
or any other benefits from any such commercial development.
IRB Review Under the Common Rule
Respondents suggested that the current regulatory structure of IRB
review under the Common Rule (45 CFR Part 46, Subpart A) addresses the
core ethical principles needed for appropriate oversight of hESC
derivation. They noted that IRB review includes a full review of the
informed consent process, as well as a determination of whether
individuals were coerced to participate in the research and whether any
undue inducements were offered to secure their participation. These
respondents urged the NIH to replace the specific standards to assure
voluntary and informed consent in the draft Guidelines with a
requirement that hESC research be reviewed and approved by an IRB, in
conformance with 45 CFR Part 46, Subpart A, as a prerequisite to NIH
funding. Respondents also requested that the NIH create a registry of
eligible hESC lines to avoid burdensome and repetitive assurances from
multiple funding applicants. The NIH agrees that the IRB system of
review under the Common Rule provides a comprehensive framework for the
review of the donation of identifiable human biological materials for
research. However, in the last several years, guidelines on hESC
research have been issued by a number of different organizations and
governments, and different practices have arisen around the country and
worldwide, resulting in a patchwork of standards. The NIH concluded
that employing the IRB review system for the donation of embryos would
not ameliorate stated concerns about variations in standards for hESC
research and would preclude the establishment of an NIH registry of
hESCs eligible for NIH funding, because there would be no NIH approval
of particular hESCs. To this end and in response to comments, these
Guidelines articulate policies and procedures that will allow the NIH
to create a Registry. These Guidelines also provide scientists who
apply for NIH funding with a specific set of standards reflecting
currently recognized ethical principles and practices specific to
embryo donation that took place on or after the issuance of the
Guidelines, while also establishing procedures for the review of
donations that took place before the effective date of the Guidelines.
Federal Funding Eligibility of Human Pluripotent Cells From Other
Sources
Respondents suggested that the allowable sources of hESCs
potentially available for Federal funding be expanded to include hESC
lines from embryos created expressly for research purposes, and lines
created, or pluripotent cells derived, following parthenogenesis or
somatic cell nuclear transfer (SCNT). The Guidelines allow for funding
of research using hESCs derived from embryos created using in vitro
fertilization (IVF) for reproductive purposes and no longer needed for
these purposes, assuming the research has scientific merit and the
embryos were donated after proper informed consent was obtained from
the donor(s). The Guidelines reflect the broad public support for
Federal funding of research using hESCs created from such embryos based
on wide and diverse debate on the topic in Congress and elsewhere. The
use of additional sources of human pluripotent stem cells proposed by
the respondents involve complex ethical and scientific issues on which
a similar consensus has not emerged. For example, the embryo-like
entities created by parthenogenesis and SCNT require women to donate
oocytes, a procedure that has health and ethical implications,
including the health risk to the donor from the course of hormonal
treatments needed to induce oocyte production.
Respondents noted that many embryos undergo Pre-implantation
Genetic Diagnosis (PGD). This may result in the identification of
chromosomal abnormalities that would make the embryos medically
unsuitable for clinical use. In addition, the IVF process may also
produce embryos that are not transferred into the uterus of a woman
because they are determined to be not appropriate for clinical use.
Respondents suggested that hESCs derived from such embryos may be
extremely valuable for scientific study, and should be considered
embryos that were created for reproductive purposes and were no longer
needed for this purpose. The NIH agrees with these comments. As in the
draft, the final Guidelines allow for the donation of embryos that have
undergone PGD.
Donation and Informed Consent
Respondents commented in numerous ways that the draft Guidelines
are too procedurally proscriptive in articulating the elements of
appropriate informed consent documentation. This over-
[[Page 32172]]
reliance on the specific details and format of the informed consent
document, respondents argued, coupled with the retroactive application
of the Guidelines to embryos already donated for research, would result
in a framework that fails to appreciate the full range of factors
contributing to the complexity of the informed consent process. For
example, respondents pointed to several factors that were precluded
from consideration by the proposed Guidelines, such as contextual
evidence of the consent process, other established governmental
frameworks (representing local and community influences), and the
changing standards for informed consent in this area of research over
time. Respondents argued that the Guidelines should be revised to allow
for a fuller array of factors to be considered in determining whether
the underlying ethical principle of voluntary informed consent had been
met. In addition to these general issues, many respondents made the
specific recommendation that all hESCs derived before the final
Guidelines were issued be automatically eligible for Federal funding
without further review, especially those eligible under prior
Presidential policy, i.e., ``grandfathered.'' The final Guidelines seek
to implement the Executive Order by issuing clear guidance to assist
this field of science to advance and reach its full potential while
ensuring adherence to strict ethical standards. To this end, the NIH is
establishing a set of conditions that will maximize ethical oversight,
while ensuring that the greatest number of ethically derived hESCs are
eligible for Federal funding. Specifically, for embryos donated in the
U.S. on or after the effective date of the Guidelines, the only way to
establish eligibility will be to either use hESCs listed on the NIH
Registry, or demonstrate compliance with the specific procedural
requirements of the Guidelines by submitting an assurance with
supporting information for administrative review by the NIH. Thus, for
future embryo donations in the United States, the Guidelines articulate
one set of procedural requirements. This responds to concerns regarding
the patchwork of requirements and guidelines that currently exist.
However, the NIH is also cognizant that in the more than a decade
between the discovery of hESCs and today, many lines were derived
consistent with ethical standards and/or guidelines developed by
various states, countries, and other entities such as the International
Society for Stem Cell Research (ISSCR) and the National Academy of
Sciences (NAS). These various policies have many common features, rely
on a consistent ethical base, and require an informed consent process,
but they differ in details of implementation. For example, some require
specific wording in a written informed consent document, while others
do not. It is important to recognize that the principles of ethical
research, e.g., voluntary informed consent to participation, have not
varied in this time period, but the requirements for implementation and
procedural safeguards employed to demonstrate compliance have evolved.
In response to these concerns, the Guidelines state that applicant
institutions wishing to use hESCs derived from embryos donated prior to
the effective date of the Guidelines may either comply with Section II
(A) of the Guidelines or undergo review by a Working Group of the
Advisory Committee to the Director (ACD). The ACD, which is a chartered
Federal Advisory Committee Act (FACA) committee, will advise NIH on
whether the core ethical principles and procedures used in the process
for obtaining informed consent for the donation of the embryo were such
that the cell line should be eligible for NIH funding. This Working
Group will not undertake a de novo evaluation of ethical standards, but
will consider the materials submitted in light of the principles and
points to consider in the Guidelines, as well as 45 CFR Part 46 Subpart
A. Rather than ``grandfathering,'' ACD Working Group review will enable
pre-existing hESCs derived in a responsible manner to be eligible for
use in NIH funded research.
In addition, for embryos donated outside the United States prior to
the effective date of these Guidelines, applicants may comply with
either Section II (A) or (B). For embryos donated outside of the United
States on or after the effective date of the Guidelines, applicants
seeking to determine eligibility for NIH research funding may submit an
assurance that the hESCs fully comply with Section II (A) or submit an
assurance along with supporting information, that the alternative
procedural standards of the foreign country where the embryo was
donated provide protections at least equivalent to those provided by
Section II (A) of these Guidelines. These materials will be reviewed by
the NIH ACD Working Group, which will recommend to the ACD whether such
equivalence exists. Final decisions will be made by the NIH Director.
This special consideration for embryos donated outside the United
States is needed because donation of embryos in foreign countries is
governed by the laws and policies of the respective governments of
those nations. Although such donations may be responsibly conducted,
such governments may not or cannot change their national donation
requirements to precisely comply with the NIH Guidelines. The NIH
believes it is reasonable to provide a means for reviewing such hESCs
because ethically derived foreign hESCs constitute an important
scientific asset for the U.S.
Respondents expressed concern that it might be difficult in some
cases to provide assurance that there was a ``clear separation''
between the prospective donor(s)' decision to create embryos for
reproductive purposes and the donor(s)' decision to donate the embryos
for research purposes. These respondents noted that policies vary at
IVF clinics, especially with respect to the degree to which connections
with researchers exist. Respondents noted that a particular clinic's
role may be limited to the provision of contact information for
researchers. A clinic that does not have any particular connection with
research would not necessarily have in place a written policy
articulating the separation contemplated by the Guidelines. Other
respondents noted that embryos that are determined not to be suitable
for medical purposes, either because of genetic defects or other
concerns, may be donated prior to being frozen. In these cases, it is
possible that the informed consent process for the donation might be
concurrent with the consent process for IVF treatment. Respondents also
noted that the initial consent for IVF may contain a general
authorization for donating embryos in excess of clinical need, even
though a more detailed consent is provided at the actual time of
donation. The NIH notes that the Guidelines specifically state that
consent should have been obtained at the time of donation, even if the
potential donor(s) had given prior indication of a general intent to
donate embryos in excess of clinical need for the purposes of research.
Accordingly, a general authorization for research donation when
consenting for reproductive treatment would comply with the Guidelines,
so long as specific consent for the donation is obtained at the time of
donation. In response to comments regarding documentation necessary to
establish a separation between clinical and research decisions, the NIH
has changed the language of the Guidelines to permit applicant
institutions to submit consent forms,
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written policies or other documentation to demonstrate compliance with
the provisions of the Guidelines. This change should provide the
flexibility to accommodate a range of practices, while adhering to the
ethical principles intended.
Some respondents want to require that the IVF physician and the
hESC researcher should be different individuals, to prevent conflict of
interest. Others say they should be the same person, because people in
both roles need to have detailed knowledge of both areas (IVF treatment
and hESC research). There is also a concern that the IVF doctor will
create extra embryos if he/she is also the researcher. As a general
matter, the NIH believes that the doctor and the researcher seeking
donation should be different individuals. However, this is not always
possible, nor is it required, in the NIH's view, for ethical donation.
Some respondents want explicit language (in the Guidelines and/or
in the consent) stating that the embryo will be destroyed when the
inner cell mass is removed. In the process of developing guidelines,
the NIH reviewed a variety of consent forms that have been used in
responsible derivations. Several had extensive descriptions of the
process and the research to be done, going well beyond the minimum
expected, yet they did not use these exact words. Given the wide
variety and diversity of forms, as well as the various policy,
statutory and regulatory obligations individual institutions face, the
NIH declines to provide exact wording for consent forms, and instead
endorses a robust informed consent process where all necessary details
are explained and understood in an ongoing, trusting relationship
between the clinic and the donor(s).
Respondents asked for clarification regarding the people who must
give informed consent for the donation of embryos for research. Some
commenters suggested that NIH should require consent from the gamete
donors, in cases where those individuals may be different than the
individuals seeking reproductive treatment. The NIH requests consent
from ``the individual(s) who sought reproductive treatment'' because
this/these individual(s) is/are responsible for the creation of the
embryo(s) and, therefore, its/their disposition. With regard to gamete
donation, the risks are associated with privacy and, as such, are
governed by requirements of the Common Rule, where applicable.
Respondents also requested clarification on the statement in the
draft Guidelines noting that ``although human embryonic stem cells are
derived from embryos, such stem cells are not themselves human
embryos.'' For the purpose of NIH funding, an embryo is defined by
Section 509, Omnibus Appropriations Act, 2009, Public Law 111-8, 3/11/
09, otherwise known as the Dickey Amendment, as any organism not
protected as a human subject under 45 CFR Part 46 that is derived by
fertilization, parthenogenesis, cloning or any other means from one or
more human gametes or human diploid cells. Since 1999, the Department
of Health and Human Services (HHS) has consistently interpreted this
provision as not applicable to research using hESCs, because hESCs are
not embryos as defined by Section 509. This long-standing
interpretation has been left unchanged by Congress, which has annually
reenacted the Dickey Amendment with full knowledge that HHS has been
funding hESC research since 2001. These guidelines therefore recognize
the distinction, accepted by Congress, between the derivation of stem
cells from an embryo that results in the embryo's destruction, for
which Federal funding is prohibited, and research involving hESCs that
does not involve an embryo nor result in an embryo's destruction, for
which Federal funding is permitted.
Some respondents wanted to ensure that potential donor(s) are
either required to put their ``extra'' embryos up for adoption before
donating them for research, or are at least offered this option. The
Guidelines require that all the options available in the health care
facility where treatment was sought pertaining to the use of embryos no
longer needed for reproductive purposes were explained to the potential
donor(s). Since not all IVF clinics offer the same services, the
healthcare facility is only required to explain the options available
to the donor(s) at that particular facility.
Commenters asked that donor(s) be made aware of the point at which
their donation decision becomes irrevocable. This is necessary because
if the embryo is de-identified, it may be impossible to stop its use
beyond a certain point. The NIH agrees with these comments and revised
the Guidelines to require that donor(s) should have been informed that
they retained the right to withdraw consent for the donation of the
embryo until the embryos were actually used to derive embryonic stem
cells or until information which could link the identity of the
donor(s) with the embryo was no longer retained, if applicable.
Medical Benefits of Donation
Regarding medical benefit, respondents were concerned that the
language of the Guidelines should not somehow eliminate a donor's
chances of benefitting from results of stem cell research. Respondents
noted that although hESCs are not currently being used clinically, it
is possible that in the future such cells might be used for the medical
benefit of the person donating them. The Guidelines are meant to
preclude individuals from donating embryos strictly for use in treating
themselves only or from donating but identifying individuals or groups
they do or do not want to potentially benefit from medical intervention
using their donated cells. While treatment with hESCs is one of the
goals of this research, in practice, years of experimental work must
still be done before such treatment might become routinely available.
The Guidelines are designed to make it clear that immediate medical
benefit from a donation is highly unlikely at this time. Importantly,
it is critical to note that the Guidelines in no way disqualify a donor
from benefitting from the medical outcomes of stem cell research and
treatments that may be developed in the future.
Monitoring and Enforcement Actions
Respondents have expressed concern about the monitoring of funded
research and the invocation of possible penalties for researchers who
do not follow the Guidelines. A grantee's failure to comply with the
terms and conditions of award, including confirmed instances of
research misconduct, may cause the NIH to take one or more enforcement
actions, depending on the severity and duration of the non-compliance.
For example, the following actions may be taken by the NIH when there
is a failure to comply with the terms and conditions of any award: (1)
Under 45 CFR 74.14, the NIH can impose special conditions on an award,
including but not limited to increased oversight/monitoring/reporting
requirements for an institution, project, or investigator; and (2)
under 45 CFR 74.62 the NIH may impose enforcement actions, including
but not limited to withholding funds pending correction of the problem,
disallowing all or part of the costs of the activity that was not in
compliance, withholding further awards for the project, or suspending
or terminating all or part of the funding for the project. Individuals
and institutions may be debarred from eligibility for all Federal
financial assistance and contracts under 2 CFR part 376 and 48
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CFR subpart 9.4, respectively. The NIH will undertake all enforcement
actions in accordance with applicable statutes, regulations, and
policies.
National Institutes of Health Guidelines for Research Using Human Stem
Cells
I. Scope of the Guidelines
These Guidelines apply to the expenditure of National Institutes of
Health (NIH) funds for research using human embryonic stem cells
(hESCs) and certain uses of induced pluripotent stem cells (See Section
IV). The Guidelines implement Executive Order 13505.
Long-standing HHS regulations for Protection of Human Subjects, 45
CFR part 46, subpart A establish safeguards for individuals who are the
sources of many human tissues used in research, including non-embryonic
human adult stem cells and human induced pluripotent stem cells. When
research involving human adult stem cells or induced pluripotent stem
cells constitutes human subject research, Institutional Review Board
review may be required and informed consent may need to be obtained per
the requirements detailed in 45 CFR part 46, subpart A. Applicants
should consult http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.
It is also important to note that the HHS regulation, Protection of
Human Subjects, 45 CFR part 46, subpart A, may apply to certain
research using hESCs. This regulation applies, among other things, to
research involving individually identifiable private information about
a living individual, 45 CFR 46.102(f). The HHS Office for Human
Research Protections (OHRP) considers biological material, such as
cells derived from human embryos, to be individually identifiable when
they can be linked to specific living individuals by the investigators
either directly or indirectly through coding systems. Thus, in certain
circumstances, IRB review may be required, in addition to compliance
with these Guidelines. Applicant institutions are urged to consult OHRP
guidances at http://www.hhs.gov/ohrp/policy/index.html#topics.
To ensure that the greatest number of responsibly derived hESCs are
eligible for research using NIH funding, these Guidelines are divided
into several sections, which apply specifically to embryos donated in
the U.S. and foreign countries, both before and on or after the
effective date of these Guidelines. Section II (A) and (B) describe the
conditions and review processes for determining hESC eligibility for
NIH funds. Further information on these review processes may be found
at http://www.NIH.gov. Sections IV and V describe research that is not
eligible for NIH funding.
These guidelines are based on the following principles:
1. Responsible research with hESCs has the potential to improve our
understanding of human health and illness and discover new ways to
prevent and/or treat illness.
2. Individuals donating embryos for research purposes should do so
freely, with voluntary and informed consent.
As directed by Executive Order 13505, the NIH shall review and
update these Guidelines periodically, as appropriate.
II. Eligibility of Human Embryonic Stem Cells for Research With NIH
Funding
For the purpose of these Guidelines, ``human embryonic stem cells
(hESCs)'' are cells that are derived from the inner cell mass of
blastocyst stage human embryos, are capable of dividing without
differentiating for a prolonged period in culture, and are known to
develop into cells and tissues of the three primary germ layers.
Although hESCs are derived from embryos, such stem cells are not
themselves human embryos. All of the processes and procedures for
review of the eligibility of hESCs will be centralized at the NIH as
follows:
A. Applicant institutions proposing research using hESCs derived
from embryos donated in the U.S. on or after the effective date of
these Guidelines may use hESCs that are posted on the new NIH Registry
or they may establish eligibility for NIH funding by submitting an
assurance of compliance with Section II (A) of the Guidelines, along
with supporting information demonstrating compliance for administrative
review by the NIH. For the purposes of this Section II (A), hESCs
should have been derived from human embryos:
1. That were created using in vitro fertilization for reproductive
purposes and were no longer needed for this purpose;
2. That were donated by individuals who sought reproductive
treatment (hereafter referred to as ``donor(s)'') and who gave
voluntary written consent for the human embryos to be used for research
purposes; and
3. For which all of the following can be assured and documentation
provided, such as consent forms, written policies, or other
documentation, provided:
a. All options available in the health care facility where
treatment was sought pertaining to the embryos no longer needed for
reproductive purposes were explained to the individual(s) who sought
reproductive treatment.
b. No payments, cash or in kind, were offered for the donated
embryos.
c. Policies and/or procedures were in place at the health care
facility where the embryos were donated that neither consenting nor
refusing to donate embryos for research would affect the quality of
care provided to potential donor(s).
d. There was a clear separation between the prospective donor(s)'s
decision to create human embryos for reproductive purposes and the
prospective donor(s)'s decision to donate human embryos for research
purposes. Specifically:
i. Decisions related to the creation of human embryos for
reproductive purposes should have been made free from the influence of
researchers proposing to derive or utilize hESCs in research. The
attending physician responsible for reproductive clinical care and the
researcher deriving and/or proposing to utilize hESCs should not have
been the same person unless separation was not practicable.
ii. At the time of donation, consent for that donation should have
been obtained from the individual(s) who had sought reproductive
treatment. That is, even if potential donor(s) had given prior
indication of their intent to donate to research any embryos that
remained after reproductive treatment, consent for the donation for
research purposes should have been given at the time of the donation.
iii. Donor(s) should have been informed that they retained the
right to withdraw consent for the donation of the embryo until the
embryos were actually used to derive embryonic stem cells or until
information which could link the identity of the donor(s) with the
embryo was no longer retained, if applicable.
e. During the consent process, the donor(s) were informed of the
following:
i. That the embryos would be used to derive hESCs for research;
ii. What would happen to the embryos in the derivation of hESCs for
research;
iii. That hESCs derived from the embryos might be kept for many
years;
iv. That the donation was made without any restriction or direction
regarding the individual(s) who may receive medical benefit from the
use of the hESCs, such as who may be the recipients of cell
transplants;
v. That the research was not intended to provide direct medical
benefit to the donor(s);
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vi. That the results of research using the hESCs may have
commercial potential, and that the donor(s) would not receive financial
or any other benefits from any such commercial development;
vii. Whether information that could identify the donor(s) would be
available to researchers.
B. Applicant institutions proposing research using hESCs derived
from embryos donated in the U.S. before the effective date of these
Guidelines may use hESCs that are posted on the new NIH Registry or
they may establish eligibility for NIH funding in one of two ways:
1. By complying with Section II (A) of the Guidelines; or
2. By submitting materials to a Working Group of the Advisory
Committee to the Director (ACD), which will make recommendations
regarding eligibility for NIH funding to its parent group, the ACD. The
ACD will make recommendations to the NIH Director, who will make final
decisions about eligibility for NIH funding.
The materials submitted must demonstrate that the hESCs were
derived from human embryos: (1) That were created using in vitro
fertilization for reproductive purposes and were no longer needed for
this purpose; and (2) that were donated by donor(s) who gave voluntary
written consent for the human embryos to be used for research purposes.
The Working Group will review submitted materials, e.g., consent
forms, written policies or other documentation, taking into account the
principles articulated in Section II (A), 45 CFR part 46, subpart A,
and the following additional points to consider. That is, during the
informed consent process, including written or oral communications,
whether the donor(s) were: (1) Informed of other available options
pertaining to the use of the embryos; (2) offered any inducements for
the donation of the embryos; and (3) informed about what would happen
to the embryos after the donation for research.
C. For embryos donated outside the United States before the
effective date of these Guidelines, applicants may comply with either
Section II (A) or (B). For embryos donated outside of the United States
on or after the effective date of the Guidelines, applicants seeking to
determine eligibility for NIH research funding may submit an assurance
that the hESCs fully comply with Section II (A) or submit an assurance
along with supporting information, that the alternative procedural
standards of the foreign country where the embryo was donated provide
protections at least equivalent to those provided by Section II (A) of
these Guidelines. These materials will be reviewed by the NIH ACD
Working Group, which will recommend to the ACD whether such equivalence
exists. Final decisions will be made by the NIH Director.
D. NIH will establish a new Registry listing hESCs eligible for use
in NIH funded research. All hESCs that have been reviewed and deemed
eligible by the NIH in accordance with these Guidelines will be posted
on the new NIH Registry.
III. Use of NIH Funds
Prior to the use of NIH funds, funding recipients should provide
assurances, when endorsing applications and progress reports submitted
to NIH for projects using hESCs, that the hESCs are listed on the NIH
registry.
IV. Research Using hESCs and/or Human Induced Pluripotent Stem Cells
That, Although the Cells May Come From Eligible Sources, Is
Nevertheless Ineligible for NIH Funding
This section governs research using hESCs and human induced
pluripotent stem cells, i.e., human cells that are capable of dividing
without differentiating for a prolonged period in culture, and are
known to develop into cells and tissues of the three primary germ
layers. Although the cells may come from eligible sources, the
following uses of these cells are nevertheless ineligible for NIH
funding, as follows:
A. Research in which hESCs (even if derived from embryos donated in
accordance with these Guidelines) or human induced pluripotent stem
cells are introduced into non-human primate blastocysts.
B. Research involving the breeding of animals where the
introduction of hESCs (even if derived from embryos donated in
accordance with these Guidelines) or human induced pluripotent stem
cells may contribute to the germ line.
V. Other Research Not Eligible for NIH Funding
A. NIH funding of the derivation of stem cells from human embryos
is prohibited by the annual appropriations ban on funding of human
embryo research (Section 509, Omnibus Appropriations Act, 2009, Pub. L.
111-8, 3/11/09), otherwise known as the Dickey Amendment.
B. Research using hESCs derived from other sources, including
somatic cell nuclear transfer, parthenogenesis, and/or IVF embryos
created for research purposes, is not eligible for NIH funding.
Dated: June 30, 2009.
Raynard S. Kington,
Acting Director, NIH.
[FR Doc. E9-15954 Filed 7-6-09; 8:45 am]
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