[Federal Register Volume 74, Number 128 (Tuesday, July 7, 2009)]
[Notices]
[Pages 32170-32175]
From the Federal Register Online via the Government Printing 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,

[[Page 32173]]

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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