and Human Services
9000 Rockville Pike
Bethesda, Maryland 20892
APPROVAL PROCESS FOR THE DOCUMENTATION OF COMPLIANCE WITH NIH GUIDELINES ON
THE USE OF HUMAN PLURIPOTENT STEM CELLS IN NIH RESEARCH PROPOSED FOR SUPPORT
UNDER GRANTS AND COOPERATIVE AGREEMENTS
Release Date: November 21, 2000
NOTICE: OD-01-003 (amended) (See Notice OD-02-007 dated November 7, 2001)
National Institutes of Health
INTRODUCTION
The only significant difference in this Notice and that published on October
16, 2000, is that there are separate descriptions of the materials to be
submitted for human pluripotent stem cells derived from embryos or fetal
tissue. The documentation to be submitted and the timetable for submission
have not changed. However, a separate discussion of the process for embryos
or fetal tissue clarifies the compliance approval process.
On August 23, 2000, the National Institutes of Health (NIH) published an
outline of procedures for the approval of the use of human pluripotent stem
cells in NIH supported intramural and extramural research
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-050.html). This
second notice details the specific procedures that must be followed by
extramural investigators proposing to use existing or seeking new NIH funds
for research using human pluripotent stem cells derived from human embryos
and human fetal tissue. These procedures are based on the NATIONAL
INSTITUTES OF HEALTH GUIDELINES FOR RESEARCH USING HUMAN PLURIPOTENT STEM
CELLS (http://www.nih.gov/news/stemcell/stemcellguidelines.htm), hereinafter
referred to as the NIH GUIDELINES, published in the Federal Register (65 FR
51976) and effective on August 25, 2000. Because the GUIDELINES contain a
few incorrect citations and other minor errors, a notice of correction (65 FR
69951) is being published on November 21, 2000. The present notice details
required procedures for research using pluripotent stem cells to be supported
under grants and cooperative agreements.
All research to be supported under NIH grants and cooperative agreements
undergoes regular scientific peer review, including the customary two-stage
process involving review by a Scientific Review Group (Study Section) and the
Advisory Council of an Institute/Center. In addition, for research that
proposes the use of human pluripotent stem cells, there will be a formal
review of documentation of compliance with the NIH GUIDELINES. This latter
review will be conducted by the Human Pluripotent Stem Cell Review Group
(HPSCRG) which is a working group of the Center for Scientific Review
Advisory Council (CSRAC). The process for documenting compliance with the
NIH GUIDELINES is separate from the grant and cooperative agreement
scientific review process. The two processes will take place in parallel in
order to ensure that all aspects of scientific review and review of
compliance are considered in a timely manner. Institutions and investigators
proposing research using human pluripotent stem cells must be mindful of the
requirements and deadlines for both processes in order to avoid delays in the
potential funding of proposed research. NIH will not provide funds or allow
existing funds to be used for research utilizing human pluripotent stem cells
derived from human embryos or human fetal tissue until appropriate approvals
have been obtained. Evidence of compliance with the NIH GUIDELINES does not
affect the scientific merit review of a grant application nor does it ensure
a favorable funding decision by the NIH.
Review of compliance with the NIH GUIDELINES is a two-stage process. Any
request proposing to use existing or seeking new NIH funds for research
utilizing human pluripotent stem cells derived from human embryos or human
fetal tissue must include the submission of compliance documentation to the
NIH. The HPSCRG members will review the submitted documentation and forward
their recommendation(s) to the CSRAC for final consideration. When the
HPSCRG receives compliance documentation in support of a request for funds
that proposes the use of a line of human pluripotent stem cells that has not
been previously reviewed by HPSCRG and recommended to, and approved by, the
CSRAC, the HPSCRG review will take place in a public meeting. Thus, although
HPSCRG will review all requests for funds, the review of compliance
documentation for the use of a cell line previously approved by the NIH will
not take place in a public meeting of the HPSCRG. The final approval of
documentation of compliance will always take place in a public meeting of the
CSRAC.
SUBMISSION OF DOCUMENTATION
Timetable
Documentation is to be submitted to the Office of Science Policy, Office of
the Director, NIH, by institutions on behalf of principal investigators. An
original and two copies of the documentation are to be submitted to:
NIH Office of Science Policy
Attention: HPSCRG
Building 1, Room 218
MSC 0166
9000 Rockville Pike
Bethesda, MD 20892
(301) 594-7741
The schedule for receipt and review by the HPSCRG and the CSRAC follows:
|-------------------------------------------------------|
|Submission Window |Materials |Review |Consideration |
|of Competing |received by |by |on by CSRAC |
|Applications(new, |Office of |HPSCRG | |
|continuation, |Science | | |
|revised, |Policy | | |
|supplements) | | | |
|------------------+------------+--------+--------------|
|January 10 to |March 15 |April |May |
|May 1 | | | |
|------------------+------------+--------+--------------|
|May 10 to |July 15 |August |September |
|September 1 | | | |
|------------------+------------+-----------------------|
|September 10 to |November 15 |December|January |
|January 2 | | | |
|-------------------------------------------------------|
Packages of documentation received by the Office of Science Policy after the
established deadlines will be held for the next cycle of HPSCRG and CSRAC
consideration.
To avoid delays, the required documentation of compliance with the NIH
GUIDELINES may need to be submitted to the Office of Science Policy in
advance of the submission of the actual grant application. Thus,
institutions planning on submitting competing grant applications whether for
standing receipt dates or special receipt dates (responses to Requests for
Applications or special Program Announcements) between January 10 and May 1
will need to submit the required documentation to the Office of Science
Policy by March 15 in order to prevent delay in the consideration of the
application. Specifically, institutions planning to submit small business
applications on April 1, individual fellowship applications on April 5, or
AIDS applications on May 1 should plan to submit the documentation to the
Office of Science Policy by March 15 in order to avoid delays in the process.
Likewise, planned submissions for August 1 (small business), August 5
(fellowships), or September 1 (AIDS) need documentation submitted on July 15
and planned submissions for December 1 (small business), December 5
(fellowships), and January 2 (AIDS) by November 15. When institutions are
submitting applications for RFAs and other special receipt dates, they must
also consider the HPSCRG schedule and submit documentation accordingly. For
administrative supplements to existing grants or proposals to use human
pluripotent stem cells in studies funded as part of existing awards without a
request for additional funds, institutions must comply with the NIH
GUIDELINES and should also submit documentation for HPSCRG review.
Investigators and institutions are advised that it may be prudent to first
contact the awarding Institute or Center to discuss the proposed
administrative supplement. If existing funds are to be used and the proposed
research constitutes a change in scope of the funded project, the principal
investigator must obtain prior approval for the change in scope from the
funding Institute/Center at NIH (see the NIH Grants Policy Statement,
(http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#chgproj) prior to
the submission of compliance material to HPSCRG. Approval of the
documentation of compliance with the NIH GUIDELINES does not ensure the
approval of the Institute/Center of an administrative supplement or for a
change in scope of the funded project.
Materials to be submitted to NIH for research on human pluripotent stem cells
derived from EMBRYOS and FETAL TISSUE are set forth below at parts I and II,
respectively.
I. HUMAN PLURIPOTENT STEM CELLS DERIVED FROM EMBRYOS
A. MATERIALS TO BE SUBMITTED TO THE OFFICE OF SCIENCE POLICY
1. Cover Page with the following information (See sample below)
a. Name of the Principal Investigator (PI).
b. Title of the grant or cooperative agreement application (See
NIH GUIDELINES, Section II.A.1.f). If part of a multicomponent
submission (for example a Program Project), include the name of
the PI, the title of the overall application, and the title(s) of
the project(s) involving the use of human pluripotent stem cells.
If a competing continuation, revised application, administrative
supplement, or existing award without a request for additional
funds, also include the grant number (for example, R01 CA123456).
c. Anticipated date of submission of the competing grant/cooperative
agreement application.
d. Name, title, telephone number, fax number, and e-mail address
of the institutional official submitting the information.
e. Signature of the institutional official.
SAMPLE COVER PAGE
Principal Investigator: Roberta Dilan, M.D.
Title of Project: “Use of Human Pluripotent Stem Cells to Treat
XYZ Disease,”
Project 4 of Renewal of Program Project,
“Diagnosis and Therapy of XYZ Disease,”
Renewal of P01 ZZ123456
(P01 Principal Investigator: James Blue, M.D., Ph.D.)
Anticipated Submission Date of Grant Application: February 1, 2001
Submitted by: University of Lakeview
Institutional Official: Eileen Smith, Ph.D.
Associate Provost for Research
University of Lakeview
555-555-1212 (voice)
555-555-2121 (fax)
smithe@lakeview.edu
2. Documentation of compliance with the NIH GUIDELINES specific to
research using human pluripotent stem cells derived from HUMAN EMBRYOS.
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 the
NIH GUIDELINES and that the institution will maintain
documentation in support of this assurance. The official’s
signature will attest that the institution has documentation (or
an assurance) from the person(s) who derived the human pluripotent
stem cells stating that the derivation process was conducted in
accordance with the NIH GUIDELINES (See NIH GUIDELINES Section
II.A.1.a). Specifically, the institutional assurance should
include a statement that the embryo(s) used to derive the
pluripotent stem cells were created through in vitro fertilization
for the purpose of fertility treatment and that the embryos had
not reached the stage at which the mesoderm is formed at the time
of donation. The assurance should also include statements that
the donation of the embryo was voluntary; that the researcher who
derived or proposed to derive the cells was a different person
than the physician who provided fertility treatment; that the
individuals undergoing fertility treatment were approached about
consent for the donation of embryos to derive pluripotent stem
cells only at the time of deciding the disposition of frozen
embryos that were in excess of clinical need; that the donor
placed no restrictions regarding the individual(s) who may be the
recipients of transplants derived from the human embryo; and that
the required informed consents and Institutional Review Board
(IRB) approval were obtained.
b. A sample of the informed consent document for the donation of the
embryo(s) for the purpose of deriving the human pluripotent stem
cells that was used in this research (with patient identifying
information removed) (See NIH GUIDELINES, Section II.A.1.b). A
description of the required elements in the informed consent
process is set forth in Section II.A.2.e of the NIH GUIDELINES.
c. An abstract of the scientific protocol that was used to derive the
human pluripotent stem cells, obtained from the person(s) who
derived the human pluripotent stem cells, describing the methods
and materials used (See NIH GUIDELINES Section II.A.1.c). Note:
This is not the abstract of the grant application.
3. Other Documentation
a. Documentation of the IRB approval of the derivation protocol (See
NIH GUIDELINES, Section II.A.1.d).
b. An assurance signed by the responsible institutional official that
the human pluripotent stem cells to be used in the proposed
research were, or will be, obtained through donation or through
payment that does not exceed the reasonable costs associated with
the transportation, processing, preservation, quality control, and
storage of the stem cells (See NIH GUIDELINES, Section II.A.1.e).
c. An assurance signed by the responsible institutional offical that
the proposed use of human pluripotent stem cells is not a class of
research that is ineligible for NIH funding as set forth in
Section III of the NIH GUIDELINES (See NIH GUIDELINES, Section
II.A.1.g).
d. The Principal Investigator’s written consent to the disclosure of
all material submitted as part of this documentation of
compliance, as necessary to carry out the public review and other
oversight procedures set forth in the NIH GUIDELINES (See NIH
GUIDELINES, Section II.A.1.h).
B. MATERIALS TO BE SUBMITTED TO THE CENTER FOR SCIENTIFIC REVIEW (CSR)
A cover letter should accompany the submission of a competing grant
application to the Division of Receipt and Referral, CSR (see
instructions in the application form for complete address and
application information), indicating that the documentation of
compliance with the NIH GUIDELINES has been, or will be, provided to the
NIH Office of Science Policy.
C. DECISIONS
HPSCRG may ask the institution to provide additional materials to
clarify the documentation of compliance with the NIH GUIDELINES. This
could delay the completion of the HPSCRG review. Following the meeting
of the CSRAC, the NIH Office of Science Policy will convey the results
of the compliance review to the principal investigator, the institution,
and the potential funding Institute or Center within the NIH.
D. FURTHER INFORMATION
Questions regarding this process should be directed to
stemcell@mail.nih.gov or call the Office of Science Policy at (301) 594-
7741.
II. HUMAN PLURIPOTENT STEM CELLS DERIVED FROM FETAL TISSUE
A. MATERIALS TO BE SUBMITTED TO THE OFFICE OF SCIENCE POLICY
1. Cover Page with the following information (See sample below)
a. Name of the Principal Investigator (PI).
b. Title of the grant or cooperative agreement application (See NIH
GUIDELINES, Section II.B.1.f). If part of a multicomponent
submission (for example a Program Project), include the name of
the PI, the title of the overall application, and the title(s) of
the project(s) involving human pluripotent stem cells. If a
competing continuation, revised application, administrative
supplement, or existing award without a request for additional
funds, also include the grant number (for example, R01 CA12345).
c. Anticipated date of submission of the competing grant/cooperative
agreement application.
d. Name, title, telephone number, fax number, and e-mail address of
the institutional official submitting the information.
e. Signature of the institutional official.
SAMPLE COVER PAGE
Principal Investigator: Roberta Dilan, M.D.
Title of Project: “Use of Human Pluripotent Stem Cells to Treat
XYZ Disease,”
Project 4 of Renewal of Program Project,
“Diagnosis and Therapy of XYZ Disease,”
Renewal of P01 ZZ123456
(P01 Principal Investigator: James Blue, M.D., Ph.D.)
Anticipated Submission Date of Grant Application: February 1, 2001
Submitted by: University of Lakeview
Institutional Official: Eileen Smith, Ph.D.
Associate Provost for Research
University of Lakeview
555-555-1212 (voice)
555-555-2121 (fax)
smithe@lakeview.edu
2. Documentation of compliance with the NIH GUIDELINES specific to
research using human pluripotent stem cells derived from FETAL
TISSUE.
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.B.2 of the
NIH GUIDELINES and that the institution will maintain
documentation in support of this assurance. The official’s
signature will attest that the institution has documentation (or
an assurance) from the person(s) who derived the human pluripotent
stem cells stating that the derivation process was conducted in
accordance with the NIH GUIDELINES (See NIH GUIDELINES Section
II.B.1.a). The assurance should also include statements that the
research complies with all of the requirements of
42 U.S.C. § 289g-1, 42 U.S.C. § 289g-2(a) and (b) and
45 C.F.R. § 46.210; that the required informed consents were
obtained; and that IRB approval was obtained.
b. A sample of the informed consent document that was used for the
donation of the human fetal tissue for the purpose of deriving the
human pluripotent stem cells (with patient identifying information
removed) (See NIH GUIDELINES, Section II.B.1.b). A description of
the required elements in the informed consent process is given at
Section II.B.2.b of the NIH GUIDELINES.
c. An abstract of the scientific protocol that was used to derive the
human pluripotent stem cells obtained from the person(s) who
derived the human pluripotent stem cells, describing the methods
and materials used (See NIH GUIDELINES Section II.B.1.c). Note:
This is not the abstract of the grant application.
3. Other Documentation
a. Documentation of IRB approval of the derivation protocol (See NIH
GUIDELINES, Section II.B.1.d).
b. An assurance signed by the responsible institutional official that
the human pluripotent stem cells to be used were, or will be,
obtained through donation or through payment that does not exceed
the reasonable costs associated with the transportation,
processing, preservation, quality control, and storage of the stem
cells (See NIH GUIDELINES, Section II.B.1.e).
c. An assurance signed by the responsible institutional official that
the proposed use of human pluripotent stem cells is not a class of
research that is ineligible for NIH funding, as set forth in
Section III of the NIH GUIDELINES (See NIH GUIDELINES, Section
II.B.1.g).
d. The Principal Investigator’s written consent to the disclosure of
all material submitted as part of this compliance documentation,
as necessary to carry out the public review and other oversight
procedures set forth in the NIH GUIDELINES (See NIH GUIDELINES,
Section II.B.1.h).
B. MATERIALS TO BE SUBMITTED TO THE CENTER FOR SCIENTIFIC REVIEW (CSR)
A cover letter should accompany the submission of a competing grant
application to the Division of Receipt and Referral, CSR (see
instructions in the application form for complete address and
application information), indicating that the documentation of
compliance with the NIH GUIDELINES has been, or will be, provided to the
NIH Office of Science Policy.
C. DECISIONS
HPSCRG may ask the institution to provide additional materials to
clarify the documentation of compliance with the NIH GUIDELINES. This
could delay the completion of the HPSCRG review. Following the meeting
of the CSRAC, the NIH Office of Science Policy will convey the results
of the compliance review to the principal investigator, the institution,
and the potential funding Institute or Center within the NIH.
D. FURTHER INFORMATION
Questions regarding this process should be directed to
stemcell@mail.nih.gov or call the Office of Science Policy at
(301) 594-7741.
Return to NIH Guide Main Index
|
|
Department of Health and Human Services |
|
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |