[Federal Register Volume 65, Number 166 (Friday, August 25, 2000)]
[Notices]
[Pages 51976-51981]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21760]
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Part IV
Department of Health and Human Services
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National Institutes of Health
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National Institutes of Health Guidelines for Research Using Human
Pluripotent Stem Cells and Notification of Request for Emergency
Clearance; Modification of OMB No. 0925-0001/Exp. 2/01, ``PHS 398
Research and Research Training Grant Applications and Related Forms'';
Notices
Federal Register / Vol. 65, No. 166 / Friday, August 25, 2000 /
Notices
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institutes of Health Guidelines for Research Using Human
Pluripotent Stem Cells
SUMMARY: The National Institutes of Health (NIH) is hereby publishing
final ``National Institutes of Health Guidelines for Research Using
Human Pluripotent Stem Cells.'' The Guidelines establish procedures to
help ensure that NIH-funded research in this area is conducted in an
ethical and legal manner.
EFFECTIVE DATE: These Guidelines are effective on August 25, 2000. The
moratorium on research using human pluripotent stem cells derived from
human embryos and fetal tissue put in place by the Director, NIH, in
January 1999, will be lifted on August 25, 2000.
SUMMARY OF PUBLIC COMMENTS ON DRAFT GUIDELINES: On December 2, 1999 (64
FR 67576), the NIH published Draft Guidelines for research involving
human pluripotent stem cells (hPSCs) in the Federal Register for public
comment. The comment period ended on February 22, 2000.
The NIH received approximately 50,000 comments from members of
Congress, patient advocacy groups, scientific societies, religious
organizations, and private citizens. This Notice presents the final
Guidelines together with NIH's response to the substantive public
comments that addressed provisions of the Guidelines.
Scope of Guidelines and General Issues
Respondents asked for clarification of terminology used in the
Guidelines and some commented that the language was not appropriate or
was too technical, particularly the informed consent sections. The NIH
agrees that these Guidelines should be clear and understandable.
Changes, including some reorganization of the sections, were made to
this end. The Guidelines are written primarily for the purpose of
informing investigators of the conditions that must be met in order to
receive NIH funding for research using hPSCs and, therefore, some
technical language is required. The Guidelines do not define the
precise language that should appear in informed consent documents
because these should be developed by the investigator/clinician
specifically for a particular study protocol or procedure for which the
consent is being sought. Existing regulatory provisions require (45 CFR
46.116) that the language in informed consent documents be
understandable to prospective participants in the study.
Respondents suggested that NIH funding for research using hPSCs
would be in violation of the DHHS appropriations law and that
derivation of hPSCs cannot be distinguished from their use. For this
reason, a number of respondents asked that the NIH withdraw the draft
Guidelines. The NIH sought the opinion of the DHHS General Counsel, who
determined that ``federally funded research that utilizes hPSCs would
not be prohibited by the HHS appropriations law prohibiting human
embryo research, because such cells are not human embryos.'' Comments
questioning this conclusion did not present information or arguments
that justify reconsideration of the conclusion.
Respondents commented that the Guidelines are too restrictive or
that there is no need for Federal Guidelines for this arena of
research. Comments asserted that federally funded research using hPSCs
should go forward without formal requirements, in the same manner as in
the private sector. In order to help ensure that the NIH-funded
research using hPSCs is conducted in an ethical and legal manner, the
NIH felt it was advisable to develop and implement guidelines. To this
end, the NIH Director convened a Working Group of the Advisory
Committee to the Director, NIH (ACD), to advise the ACD on the
development of guidelines and an oversight process for research
involving hPSCs. The NIH Director charged the Working Group with
developing appropriate guidelines to govern research involving the
derivation and use of hPSCs from fetal tissue and research involving
the use of hPSCs derived from human embryos that are in excess of
clinical need.
Respondents commented regarding the sources of stem cells. Some
respondents stated that research on hPSCs was unnecessary because stem
cells from adults, umbilical cords, and placentas could be used
instead. Other respondents asked the NIH to restrict Federal funding
for hPSC research to those cells derived from fetal and adult tissue
but not embryos. Other respondents asked that the Guidelines encompass
research using stem cells from adult tissues.
As stated under Section I. Scope of Guidelines, the Guidelines
apply to the use of NIH funds for research using hPSCs derived from
human embryos or human fetal tissue. The Guidelines do not impose
requirements on Federal funding of research involving stem cells from
human adults, umbilical cords, or placentas.
Given the enormous potential of stem cells to the development of
new therapies for the most devastating diseases, it is important to
simultaneously pursue all lines of promising research. It is possible
that no single source of stem cells is best or even suitable/usable for
all therapies. Different types or sources of stem cells may be optimal
for treatment of specific conditions. In order to determine the very
best source of many of the specialized cells and tissues of the body
for new treatments and even cures, it is vitally important to study the
potential of adult stem cells for comparison to that of hPSCs derived
from embryos and fetuses. Unless all stem cell types are studied, the
differences between adult stem cells and embryo and fetal-derived hPSCs
will not be known.
Moreover, there is evidence that adult stem cells may have more
limited potential than hPSCs. First, stem cells for all cell and tissue
types have not yet been found in the adult human. Significantly,
cardiac stem cells or pancreatic islet stem cells have not been
identified in adult humans.
Second, stem cells in adults are often present in only minute
quantities, are difficult to isolate and purify, and their numbers may
decrease with age. For example, brain cells from adults that may be
neural stem cells have been obtained only by removing a portion of the
brain of an adult with epilepsy, a complex and invasive procedure that
carries the added risk of further neurological damage. Any attempt to
use stem cells from a patient's own body for treatment would require
that stem cells would first have to be isolated from the patient and
then grown in culture in sufficient numbers to obtain adequate
quantities for treatment. This would mean that for some rapidly
progressing disorders, there may not be sufficient time to grow enough
cells to use for treatment.
Third, in disorders that are caused by a genetic defect, the
genetic error likely would be present in the patient's stem cells,
making cells from such a patient inappropriate for transplantation. In
addition, adult stem cells may contain more DNA abnormalities caused by
exposure to daily living, including sunlight, toxins, and errors made
during DNA replication than will be found in fetal or embryonic hPSCs.
Fourth, there is evidence that stem cells from adults may not have
the same capacity to multiply as do younger cells. These potential
weaknesses may limit the usefulness of adult stem cells.
[[Page 51977]]
Respondents were concerned that these are guidelines and not
requirements or regulations. Although these are guidelines and not
regulations, they prescribe the documentation and assurances that must
accompany requests for NIH funding for research utilizing hPSCs. If the
funding requests do not contain the prescribed information, funding for
hPSC research will not be provided. Compliance with the Guidelines will
be imposed as a condition of grant award.
Respondents commented that there had not been enough widespread
public disclosure/discussion of this research or the Guidelines. Prior
to the development of draft Guidelines, there were two Congressional
hearings on hPSCs. In a further effort to ensure substantial discussion
and comment, the NIH convened a Working Group of the Advisory Committee
to the Director, NIH (ACD), to advise the ACD on the development of
these Guidelines. The Working Group was composed of scientists,
patients and patient advocates, ethicists, clinicians, and lawyers. The
Working Group met in public session on April 8, 1999, and heard from
members of the public, as well as professional associations and
Congress. In developing the draft Guidelines, the NIH also considered
advice from the National Bioethics Advisory Commission (NBAC). Draft
Guidelines were published for public comment in the Federal Register on
December 2, 1999, for 60 days, and, in response to public interest, the
comment period was extended an additional 28 days. Approximately 50,000
comments were received. NIH issued a national press release announcing
the Federal Register notice and many of the Nation's newspapers carried
articles on this area of research and on the Guidelines. Patient
groups, scientific societies, and religious organizations convened
meetings and discussion groups and disseminated materials about this
area of research and about the Guidelines.
Comment was received about whether the Guidelines apply to hPSC
lines developed outside of the United States. The Guidelines make no
distinction based upon the country in which an hPSC line is developed.
All lines to be used in hPSC cell research funded by NIH must meet the
same requirements.
Derivation and Use of hPSCs From Fetal Tissue
Respondents made the point that the NIH has specified certain
requirements for the use of human fetal tissue to derive hPSCs in
addition to those imposed on other areas of human fetal tissue
research. These respondents suggested that the section of the
Guidelines pertaining to fetal tissue sources be omitted. In order to
ensure uniformity in NIH's oversight of research using hPSCs, the
Guidelines were extended to govern hPSCs derived from both human
embryos and fetal tissue.
Use of hPSCs Derived From Human Embryos
Respondents suggested that the Guidelines refer to ``fertility
treatment'' rather than to ``infertility treatment'' in order to
clarify that they allow the use of human embryos from treatments that
employ assisted reproductive technologies to facilitate reproduction in
fertile, as well as in infertile, individuals. The Guidelines have been
changed accordingly.
Respondents suggested dropping the word ``early'' throughout the
document or more clearly defining ``early.'' The word ``early'' in
reference to human embryos has been deleted; the Guidelines make it
clear that NIH funding of research using hPSCs derived in the private
sector from human embryos can involve only embryos that have not
reached the stage at which the mesoderm is formed.
Some respondents were concerned that embryos might be created for
research purposes. Other respondents stated there should be no
distinction between embryos created for research purposes and those
created for fertility treatment. Investigators seeking NIH funds for
research using hPSCs are required to provide documentation, prior to
the award of any NIH funds, that embryos were created for the purposes
of fertility treatment. President Clinton, many members of Congress,
the NIH Human Embryo Research Panel, and the NBAC have all embraced the
distinction between embryos created for research purposes and those
created for reproductive purposes.
Respondents were concerned about the creation of a ``black market''
for human embryos, and expressed concerns that individuals will be
coerced into donating embryos. The Guidelines state that there can be
no incentives for donation and that a decision to donate must be made
free of coercion. In addition, the Guidelines set forth conditions that
will help ensure all donations are voluntary. For example, with regard
to hPSCs derived from embryos, research using Federal funds may only be
conducted if the cells were derived from frozen embryos that were
created for the purpose of fertility treatment and that were in excess
of clinical need.
Respondents commented on the requirement that human embryos be
frozen in order to qualify for derivation of hPSCs to be used in NIH-
funded research. Respondents suggested that the freezing requirement
would preclude the use of hPSCs derived from embryos that are
genetically and chromosomally abnormal, since such embryos are usually
not frozen for reproductive purposes. While the NIH acknowledges that
research on hPSCs derived from such embryos could yield important
scientific information, limiting research to hPSCs derived from frozen
human embryos will help ensure that the decision to donate the embryo
for hPSC research is distinct and separate from the fertility
treatment.
Financial Issues
Respondents expressed concern regarding the sale of fetal tissue
for profit and whether hPSC research would encourage such activity.
Respondents also were concerned about whether clinics or doctors would
profit from the derivation of hPSCs and/or their sale. Section 498B of
the Public Health Service Act prohibits any individual from knowingly
acquiring or selling human fetal tissue for ``valuable consideration.''
In addition, the Guidelines prohibit any inducement for the donation of
human embryos for research purposes. The Guidelines also call for an
assurance that the hPSCs to be used in NIH-funded research were
obtained through a donation or through a payment that does not exceed
the reasonable costs associated with the transportation, processing,
preservation, quality control and storage of the hPSCs. All grantees
must sign an assurance that they are in compliance with all applicable
Federal, State, and local laws. Each funded research institution is
responsible for monitoring compliance by individual investigators with
any such applicable laws.
Respondents questioned the prohibition against embryo donors
benefitting financially from their donation. This clause was retained
in the final Guidelines to help ensure that the donating individuals
are offered no inducements to donate and that all donations are
voluntary.
Respondents suggested that the Guidelines be strengthened to
include a waiver of intellectual property rights. This proposed change
would be inconsistent with 45 CFR 46.116 of the regulation for the
protection of human subjects of research, which provides that no
informed consent may include
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language through which the subject waives or appears to waive any of
the subject's legal rights.
Respondents questioned the reference in the requirements for
informed consent related to the commercial potential of donated
material. The paragraphs providing for disclosure in the informed
consent of the possibility that the donated material could have
commercial potential were modified. The reference in these paragraphs
to ``donated material'' did not accurately reflect the intent of the
provision. The Guidelines now make clear that the ``results of research
on the human pluripotent stem cells may have commercial potential.''
Ineligible Research
Respondents objected to the areas of research that the NIH has
deemed ineligible, particularly research that is not restricted by
statute or regulation, such as research utilizing hPSCs that were
derived using somatic cell nuclear transfer, i.e., the transfer of a
human somatic cell nucleus into a human egg. The NIH determined that,
at this time, research using hPSCs derived from such sources has not
received adequate discussion and consideration by the public and is,
therefore, ineligible for NIH funding.
Separation of Fertility Treatment and Abortion From Research
Respondents were concerned that hPSC research would encourage
abortion. The law and the Guidelines guard against encouraging abortion
by requiring that the decision to have an abortion be made apart from
and prior to the decision to donate tissue.
Respondents objected to the condition in the Guidelines that the
fertility physician could not be the same person as the researcher
deriving stem cells. Some respondents stated that the Institutional
Review Board (IRB) or an independent physician would be able to guard
against this conflict of interest. The restriction was designed so that
the person treating the individuals seeking fertility treatment, who is
involved in decisions such as how many embryos to produce, is not the
person seeking to derive hPSCs. This separation will help ensure that
embryos will not be created in numbers greater than necessary for
fertility treatment.
Respondents suggested that the clauses regarding donation of fetal
tissue or human embryos for derivation of stem cells for eventual use
in transplantation be changed explicitly to prevent directed donation.
This change has been made.
Identifiers
Respondents were concerned about removing identifiers. There was
concern that the investigator would not be able to document compliance
with the Guidelines requirements without identifiers, or that the
removal of identifiers would make it impossible to conduct certain
genetic studies or develop therapeutic materials. The Guidelines have
been modified to clarify that the term ``identifier'' refers to any
information from which the donor(s) can be identified, directly or
through identifiers linked to the donors. However, since information
identifying the donor(s) may be necessary if the tissue or cells are to
be used in transplantation, the Guidelines have also been modified to
state that the informed consent should notify donor(s) whether or not
identifiers will be retained.
Respondents commented that DNA is an identifier and that all donors
of human embryos or fetal tissue should be told that identifiers such
as DNA will be retained with the samples. Although DNA can be used to
determine the individual from whom a tissue sample was taken, this can
be done only when one has a sample from both the tissue in question and
the putative donor; it cannot be used to identify an individual out of
a population. Moreover, it is difficult to identify a donor using
tissue derived from a fetus or embryo, since the tissue is not
genetically identical to the donor.
Informed Consent and IRB Review
Respondents asked why investigators were expected to provide
documentation of IRB review of derivation from human embryos, but not
for derivation from fetal tissue. Respondents suggested that the
requirements be changed so that protocols for both sources of hPSCs
must be approved by an IRB. The Guidelines have been changed to make
clear that the IRB review requirements regarding the derivation of
cells from fetal tissue and human embryos are the same.
Comment was received expressing concern that the informed consent
explicitly state that the donor will have no dispositional authority
over derived pluripotent stem cells. The Guidelines state that donation
of human embryos should have been made without any restriction
regarding the individual(s) who may be the recipient of the cells
derived from the hPSCs for transplantation. Such a statement is
consistent with the statutory provision applicable to the donor
informed consent for the use of fetal tissue for transplantation. The
Guidelines now provide for the inclusion of a statement to this effect
in the informed consent.
Respondents urged that the Guidelines be revised to remove the
prohibition on potential donors receiving information regarding
subsequent testing of donated tissue in the situation when physicians
deem disclosure to be in the donors' best interest. This change has
been made.
Respondents requested clarification regarding the persons from whom
consent for donation of embryos for research must be obtained. The
Guidelines call for informed consent from individual(s) who have sought
fertility treatment. Only the individual(s) who were part of the
decision to create the embryo for reproductive purposes should have
been part of the decision to donate for the derivation of hPSCs.
Respondents urged that fertility clinics should be able to discuss
with patients the option of donating embryos for research at the
beginning of the IVF process. The Guidelines do not delineate the
timeframe during which the general option of donating embryos for
research can be discussed. However, according to the Guidelines,
obtaining consent for donation of embryos for the purpose of deriving
hPSCs should not occur until after the embryos are determined to be in
``excess of clinical need.''
Oversight
Respondents stated that the NIH's oversight in this area of
research was very important to the legal and ethical conduct of this
research, and asked for more information regarding the oversight
process. Information about the operations of the Human Pluripotent Stem
Cell Review Group (HPSCRG) can be found in the final Guidelines and on
the NIH Web page.
Respondents were concerned about whether and how NIH would monitor
research after a researcher receives NIH funds. Compliance with the
Guidelines will be largely determined prior to the award of funds.
Follow-up to ensure continued compliance with the Guidelines will be
conducted in the same manner as for all other conditions of all other
NIH grant awards. It is the responsibility of the investigator to file
progress reports, and it is the responsibility of the funded
institution to ensure compliance with the NIH Guidelines. NIH staff
will also monitor the progress of these investigators as part of their
regular duties.
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Respondents asked about penalties for not following the Guidelines.
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
increased oversight/monitoring/reporting requirements for an
institution, project or investigator; and (2) under 45 CFR 74.62, if a
grantee materially fails to comply with the terms and conditions of the
award, the NIH may withhold funds pending correction of the problem or,
pending more severe enforcement action, disallow all or part of the
costs of the activity that was not in compliance, withhold further
awards for the project, or suspend or terminate 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 45 CFR Part 76 and 48 CFR Subpart 9.4, respectively. Because
these sanctions pertain to all conditions of grant award, the NIH did
not reiterate them in the Guidelines.
Respondents suggested that the HPSCRG hold periodic Stem Cell
Policy Conferences (similar to the Gene Therapy Policy Conferences
conducted by the Recombinant DNA Advisory Committee (``RAC'')) in order
to solicit and consider public comment from interested parties on the
scientific, medical, legal, and ethical issues arising from stem cell
research. Members of the HPSCRG will serve as a resource for
recommending to the NIH any need for Human Pluripotent Stem Cell Policy
Conferences.
Other Changes
Because compliance materials may be made public prior to funding
decisions, we have added a sentence requiring the principal
investigator's written consent to the disclosure of such material
necessary to carry out public review and other oversight procedures.
The draft Guidelines required HPSCRG review of proposals from
investigators planning to derive hPSCs from fetal tissue. Because the
Guidelines address proposals for NIH funding for the use of hPSCs, this
requirement has been removed from the Guidelines.
The text of the final Guidelines follows.
National Institutes of Health Guidelines for Research Using Human
Pluripotent Stem Cells
I. Scope of Guidelines
These Guidelines apply to the expenditure of National Institutes of
Health (NIH) funds for research using human pluripotent stem cells
derived from human embryos (technically known as human embryonic stem
cells) or human fetal tissue (technically known as human embryonic germ
cells). For purposes of these Guidelines, ``human pluripotent stem
cells'' are cells that are self-replicating, are derived from human
embryos or human fetal tissue, and are known to develop into cells and
tissues of the three primary germ layers. Although human pluripotent
stem cells may be derived from embryos or fetal tissue, such stem cells
are not themselves embryos. NIH research funded under these Guidelines
will involve human pluripotent stem cells derived: (1) From human fetal
tissue; or (2) from human embryos that are the result of in vitro
fertilization, are in excess of clinical need, and have not reached the
stage at which the mesoderm is formed.
In accordance with 42 Code of Federal Regulations (CFR) 52.4, these
Guidelines prescribe the documentation and assurances that must
accompany requests for NIH funding for research using human pluripotent
stem cells from: (1) Awardees who want to use existing funds; (2)
awardees requesting an administrative or competing supplement; and (3)
applicants or intramural researchers submitting applications or
proposals. NIH funds may be used to derive human pluripotent stem cells
from fetal tissue. NIH funds may not be used to derive human
pluripotent stem cells from human embryos. These Guidelines also
designate certain areas of human pluripotent stem cell research as
ineligible for NIH funding.
II. Guidelines for Research Using Human Pluripotent Stem Cells That
Is Eligible for NIH Funding
A. Utilization of Human Pluripotent Stem Cells Derived From Human
Embryos
1. Submission to NIH
Intramural or extramural investigators who are intending to use
existing funds, are requesting an administrative supplement, or are
applying for new NIH funding for research using human pluripotent stem
cells derived from human embryos must submit to NIH the following:
a. An assurance signed by the responsible institutional official
that the pluripotent stem cells were derived from human embryos in
accordance with the conditions set forth in section II.A.2 of these
Guidelines and that the institution will maintain documentation in
support of the assurance;
b. A sample informed consent document (with patient identifier
information removed) and a description of the informed consent process
that meet the criteria for informed consent set forth in section
II.A.2.e of these Guidelines;
c. An abstract of the scientific protocol used to derive human
pluripotent stem cells from an embryo;
d. Documentation of Institutional Review Board (IRB) approval of
the derivation protocol;
e. An assurance that the stem cells to be used in the research were
or will be obtained through a donation or through a payment that does
not exceed the reasonable costs associated with the transportation,
processing, preservation, quality control and storage of the stem
cells;
f. The title of the research proposal or specific subproject that
proposes the use of human pluripotent stem cells;
g. An assurance that the proposed research using human pluripotent
stem cells is not a class of research that is ineligible for NIH
funding as set forth in section III of these Guidelines; and
h. The Principal Investigator's written consent to the disclosure
of all material submitted under Paragraph A.1 of this section, as
necessary to carry out the public review and other oversight procedures
set forth in section IV of these Guidelines.
2. Conditions for the Utilization of Human Pluripotent Stem Cells
Derived From Human Embryos
Studies utilizing pluripotent stem cells derived from human embryos
may be conducted using NIH funds only if the cells were derived
(without Federal funds) from human embryos that were created for the
purposes of fertility treatment and were in excess of the clinical need
of the individuals seeking such treatment.
a. To ensure that the donation of human embryos in excess of the
clinical need is voluntary, no inducements, monetary or otherwise,
should have been offered for the donation of human embryos for research
purposes. Fertility clinics and/or their affiliated laboratories should
have implemented specific written policies and practices to ensure that
no such inducements are made available.
b. There should have been a clear separation between the decision
to create embryos for fertility treatment and the decision to donate
human embryos in excess of clinical need for research purposes to
derive pluripotent stem cells. Decisions related to the creation of
embryos for fertility treatment should have been made free
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from the influence of researchers or investigators proposing to derive
or utilize human pluripotent stem cells in research. To this end, the
attending physician responsible for the fertility treatment and the
researcher or investigator deriving and/or proposing to utilize human
pluripotent stem cells should not have been one and the same person.
c. To ensure that human embryos donated for research were in excess
of the clinical need of the individuals seeking fertility treatment and
to allow potential donors time between the creation of the embryos for
fertility treatment and the decision to donate for research purposes,
only frozen human embryos should have been used to derive human
pluripotent stem cells. In addition, individuals undergoing fertility
treatment should have been approached about consent for donation of
human embryos to derive pluripotent stem cells only at the time of
deciding the disposition of embryos in excess of the clinical need.
d. Donation of human embryos should have been made without any
restriction or direction regarding the individual(s) who may be the
recipients of transplantation of the cells derived from the human
pluripotent stem cells.
e. Informed Consent
Informed consent should have been obtained from individuals who
have sought fertility treatment and who elect to donate human embryos
in excess of clinical need for human pluripotent stem cell research
purposes. The informed consent process should have included discussion
of the following information with potential donors, pertinent to making
the decision whether or not to donate their embryos for research
purposes.
Informed consent should have included:
(i) A statement that the embryos will be used to derive human
pluripotent stem cells for research that may include human
transplantation research;
(ii) A statement that the donation is made without any restriction
or direction regarding the individual(s) who may be the recipient(s) of
transplantation of the cells derived from the embryo;
(iii) A statement as to whether or not information that could
identify the donors of the embryos, directly or through identifiers
linked to the donors, will be removed prior to the derivation or the
use of human pluripotent stem cells;
(iv) A statement that derived cells and/or cell lines may be kept
for many years;
(v) Disclosure of the possibility that the results of research on
the human pluripotent stem cells may have commercial potential, and a
statement that the donor will not receive financial or any other
benefits from any such future commercial development;
(vi) A statement that the research is not intended to provide
direct medical benefit to the donor; and
(vii) A statement that embryos donated will not be transferred to a
woman's uterus and will not survive the human pluripotent stem cell
derivation process.
f. Derivation protocols should have been approved by an IRB
established in accord with 45 CFR 46.107 and 46.108 or FDA regulations
at 21 CFR 56.107 and 56.108.
B. Utilization of Human Pluripotent Stem Cells Derived From Human Fetal
Tissue
1. Submission to NIH
Intramural or extramural investigators who are intending to use
existing funds, are requesting an administrative supplement, or are
applying for new NIH funding for research using human pluripotent stem
cells derived from fetal tissue must submit to NIH the following:
a. An assurance signed by the responsible institutional official
that the pluripotent stem cells were derived from human fetal tissue in
accordance with the conditions set forth in section II.A.2 of these
Guidelines and that the institution will maintain documentation in
support of the assurance;
b. A sample informed consent document (with patient identifier
information removed) and a description of the informed consent process
that meet the criteria for informed consent set forth in section
II.B.2.b of these Guidelines;
c. An abstract of the scientific protocol used to derive human
pluripotent stem cells from fetal tissue;
d. Documentation of IRB approval of the derivation protocol;
e. An assurance that the stem cells to be used in the research were
or will be obtained through a donation or through a payment that does
not exceed the reasonable costs associated with the transportation,
processing, preservation, quality control and storage of the stem
cells;
f. The title of the research proposal or specific subproject that
proposes the use of human pluripotent stem cells;
g. An assurance that the proposed research using human pluripotent
stem cells is not a class of research that is ineligible for NIH
funding as set forth in section III of these Guidelines; and
h. The Principal Investigator's written consent to the disclosure
of all material submitted under Paragraph B.1 of this section, as
necessary to carry out the public review and other oversight procedures
set forth in section IV of these Guidelines.
2. Conditions for the Utilization of Human Pluripotent Stem Cells
Derived From Fetal Tissue.
a. Unlike pluripotent stem cells derived from human embryos, DHHS
funds may be used to support research to derive pluripotent stem cells
from fetal tissue, as well as for research utilizing such cells. Such
research is governed by Federal statutory restrictions regarding fetal
tissue research at 42 U.S.C. 289g-2(a) and the Federal regulations at
45 CFR 46.210. In addition, because cells derived from fetal tissue at
the early stages of investigation may, at a later date, be used in
human fetal tissue transplantation research, it is the policy of NIH to
require that all NIH-funded research involving the derivation or
utilization of pluripotent stem cells from human fetal tissue also
comply with the fetal tissue transplantation research statute at 42
U.S.C. 289g-1.
b. Informed Consent
As a policy matter, NIH-funded research deriving or utilizing human
pluripotent stem cells from fetal tissue should comply with the
informed consent law applicable to fetal tissue transplantation
research (42 U.S.C. 289g-1) and the following conditions. The informed
consent process should have included discussion of the following
information with potential donors, pertinent to making the decision
whether to donate fetal tissue for research purposes.
Informed consent should have included:
(i) A statement that fetal tissue will be used to derive human
pluripotent stem cells for research that may include human
transplantation research;
(ii) A statement that the donation is made without any restriction
or direction regarding the individual(s) who may be the recipient(s) of
transplantation of the cells derived from the fetal tissue;
(iii) A statement as to whether or not information that could
identify the donors of the fetal tissue, directly or through
identifiers linked to the donors, will be removed prior to the
derivation or the use of human pluripotent stem cells;
(iv) A statement that derived cells and/or cell lines may be kept
for many years;
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(v) Disclosure of the possibility that the results of research on
the human pluripotent stem cells may have commercial potential, and a
statement that the donor will not receive financial or any other
benefits from any such future commercial development; and
(vi) A statement that the research is not intended to provide
direct medical benefit to the donor.
c. Derivation protocols should have been approved by an IRB
established in accord with 45 CFR 46.107 and 46.108 or FDA regulations
at 21 CFR 56.107 and 56.108.
III. Areas of Research Involving Human Pluripotent Stem Cells That
Are Ineligible for NIH Funding
Areas of research ineligible for NIH funding include:
A. The derivation of pluripotent stem cells from human embryos;
B. Research in which human pluripotent stem cells are utilized to
create or contribute to a human embryo;
C. Research utilizing pluripotent stem cells that were derived from
human embryos created for research purposes, rather than for fertility
treatment;
D. Research in which human pluripotent stem cells are derived using
somatic cell nuclear transfer, i.e., the transfer of a human somatic
cell nucleus into a human or animal egg;
E. Research utilizing human pluripotent stem cells that were
derived using somatic cell nuclear transfer, i.e., the transfer of a
human somatic cell nucleus into a human or animal egg;
F. Research in which human pluripotent stem cells are combined with
an animal embryo; and
G. Research in which human pluripotent stem cells are used in
combination with somatic cell nuclear transfer for the purposes of
reproductive cloning of a human.
IV. Oversight
A. The NIH Human Pluripotent Stem Cell Review Group (HPSCRG) will
review documentation of compliance with the Guidelines for funding
requests that propose the use of human pluripotent stem cells. This
working group will hold public meetings when a funding request proposes
the use of a line of human pluripotent stem cells that has not been
previously reviewed and approved by the HPSCRG.
B. In the case of new or competing continuation (renewal) or
competing supplement applications, all applications shall be reviewed
by HPSCRG and for scientific merit by a Scientific Review Group. In the
case of requests to use existing funds or applications for an
administrative supplement or in the case of intramural proposals,
Institute or Center staff should forward material to the HPSCRG for
review and determination of compliance with the Guidelines prior to
allowing the research to proceed.
C. The NIH will compile a yearly report that will include the
number of applications and proposals reviewed and the titles of all
awarded applications, supplements or administrative approvals for the
use of existing funds, and intramural projects.
D. Members of the HPSCRG will also serve as a resource for
recommendations to the NIH with regard to any revisions to the NIH
Guidelines for Research Using Human Pluripotent Stem Cells and any need
for human pluripotent stem cell policy conferences.
Dated: August 17, 2000.
Ruth L. Kirschstein,
Principal Deputy Director, NIH.
[FR Doc. 00-21760 Filed 8-23-00; 8:45 am]
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