Current through Register Vol. 48, No. 12, March 22, 2024
All grantees shall comply with the following requirements in
the course of performing stem cell research funded by a grant under this
Part:
a) All research shall be
undertaken according to the National Academies of Science Guidelines for Human
Embryonic Stem Cell Research. The research shall be approved by the ESCRO
committee and submitted with the application. Any changes from the National
Academies of Science Guidelines for Human Embryonic Stem Cell Research shall be
submitted to the Department prior to implementation to assure compliance with
this Part and the grant agreement. Any use of human embryonic stem cells shall
be consistent with the National Academies of Science Guidelines for Human
Embryonic Stem Cell Research.
b)
All research shall at all times comply with all applicable federal laws,
including, but not limited to, the Occupational Health and Safety Act and
HIPAA, and the following federal regulations: Institutional Animal Care and Use
Committee (IACUC) and Attending Veterinarian and Adequate Veterinarian Care.
Grantees shall comply with the U.S. Department of Health and Human Services
regulations titled Protection of Human Subjects and the U.S. Department of
Agriculture regulations titled Attending Veterinarian and Adequate Veterinarian
Care and Institutional Animal Care and Use committee (IACUC) (see Section
995.15
).
c) Grantees shall be responsible
for supervising their investigators to ensure that they conduct themselves in
accordance with the grant agreement and professional standards.
d) The project period shall be up to 24
months.
e) Grantees shall obtain
the informed consent of all research donors, patients and participants,
including a new consent from individuals who had indicated their intent to
donate to research any blastocysts that remain after clinical care at the time
of the original harvesting. Donors shall be informed that they retain the right
to withdraw consent until the blastocysts are actually used in cell line
derivation. A research project's informed consent procedures shall satisfy each
of the following requirements:
1) In seeking
informed consent, the following information shall be provided to each research
donor, patient or participant:
A) A statement
that the study involves research, an explanation of the purposes of the
research and the expected duration of the subject's participation, a
description of the procedures to be followed, and identification of any
procedures that are experimental;
B) A description of any reasonably
foreseeable risks or discomforts to the donor;
C) A description of any benefits to the donor
or to others that may reasonably be expected from the research;
D) A disclosure of appropriate alternative
options pertaining to use of the embryos;
E) A statement describing the extent, if any,
to which confidentiality of records identifying the donor will be
maintained;
F) For research
involving more than minimal risk, an explanation as to whether any compensation
and an explanation as to whether any medical treatments are available if injury
occurs and, if so, what they consist of, or where further information may be
obtained;
G) An explanation of whom
to contact for answers to pertinent questions about the research and research
donors' rights, and whom to contact in the event of a research-related injury
to the donor; and
H) A statement
that participation or donation is voluntary; that refusal to participate and/or
donate will involve no penalty or loss of benefits to which the donor is
otherwise entitled; and that the donor may discontinue participation at any
time without penalty or loss of benefits to which the donor is otherwise
entitled.
2) When
appropriate, the following additional elements of information shall also be
provided to each research donor:
A)
Anticipated circumstances under which the donor's participation in the research
may be terminated without the donor's consent;
B) The consequences of the donor's decision
to withdraw from the research, and procedures for the donor's orderly
termination of participation; or
C)
Significant new findings developed during the course of the research that may
relate to the donor's willingness to continue participation.
3) The grantee shall develop the
precise form of the informed consent specifically for the particular study
protocol or procedure for which the consent is being sought, and the informed
consent form shall be approved by the grantee's ESCRO committee.
4) The language in the informed consent shall
be clear and understandable.
5)
When donor gametes have been used in the in vitro fertilization process,
resulting blastocysts shall not be used for research without consent of all
gamete donors.
6) The informed
consent shall otherwise conform to the requirements for research funded by the
National Institutes of Health and be consistent with the Guidelines for Human
Embryonic Stem Cell Research published by the National Academies of Science
(see Section 995.15).
f)
Financial Incentives Prohibited
No cash or in-kind payments shall be provided for the
solicitation or donation of blastocysts, gametes or somatic cells for research
purposes or of somatic cells for use in nuclear transfers.
g) Standards of Clinical Care
1) Consenting or refusing to donate gametes
or blastocysts for research shall not affect or alter in any way the quality of
care provided to prospective donors. Clinical staff shall provide care to
patients without prejudice regarding their decisions about disposition of their
embryos.
2) Researchers shall not
ask members of the infertility treatment team to generate more oocytes than
necessary for the optimal chance of reproductive success. An infertility clinic
or other third party responsible for obtaining consent or collecting materials
is not to pay for or be paid for the material obtained (except for specifically
defined cost-based reimbursements and payments for professional
services).
h) Privacy
and Confidentiality
1) Grantees shall at all
times ensure that donors' personal health information is protected and kept
confidential. Investigators and institutions shall comply with applicable laws,
including, but not limited to, HIPAA.
2) Grantees shall ensure that authorizations
are received from donors, as required by HIPAA, for the confidential
transmission of personal health information to repositories or to investigators
who are using embryonic stem cell lines derived from donated
materials.
3) When the FDA requires
that the identity of the donor source be preserved, investigators and
institutions shall ensure that the confidentiality of the donor is protected;
that the donor understands that the donor's identity will be maintained; and
that, where applicable, human subject protections as defined in HIPAA are
followed.
i) Derivation
of Stem Cell Lines
1) Requests from the
investigators to the ESCRO committee for permission to attempt derivation of
new embryonic stem cell lines from donated embryos or blastocysts or from any
other source or by another procedure not previously approved by the IRB shall
include the IRB's written approval of the procurement process.
2) The investigator shall present the
scientific rationale for the need to generate new embryonic stem cell lines, by
whatever means, to the ESCRO committee, and the investigators shall justify the
basis for the numbers of embryos and blastocysts needed.
3) Blastocysts made using nuclear transfer
(whether produced with human or nonhuman oocytes) and parthenogenetic or
androgenetic human embryos shall not be transferred to a human or nonhuman
uterus and shall not be cultured as intact embryos in vitro.
4) Cells shall not be extracted from
blastocysts more than 12 days after cell division begins, not counting any time
during which the blastocysts or cells have been stored frozen.
5) Investigators shall document how they will
characterize, validate, store and distribute the new embryonic stem cell lines
and how they will maintain the confidentiality of any coded or identifiable
information associated with the lines.
j) Storage and Distribution of Stem Cell
Lines
1) Cell lines derived or modified in
any way with IRMI grant funds shall be deposited in a bank in a timely manner
as defined in the grant agreement. Grantees shall allow stem cell lines to be
shared with other investigators.
2)
Grantees that are banking or plan to bank embryonic stem cell lines shall
establish uniform guidelines to ensure that records are maintained about all
aspects of cell culture, and shall establish uniform tracking systems and
common guidelines for distribution of cells.
3) Grantees engaged in obtaining and storing
embryonic cell lines shall:
A) Create a
committee for policy and oversight purposes and create clear and standardized
protocols for banking and withdrawals.
B) Establish documentation requirements for
investigators and sites that deposit cell lines, including:
i) Providing a copy of the donor consent
form;
ii) Providing proof of
written approval of the procurement process by the depositor's IRB and the
grantee's IRB;
iii) Providing
available medical information on the donors, including results of infectious
disease screening;
iv) Providing
available clinical, observational or diagnostic information about the
donors;
v) Providing critical
information about culture conditions (such as media, cell passage and safety
information); and
vi) Providing
available cell lines characterization (such as karyotype and genetic
markers).
C) Establish a
secure system for protecting the privacy of donors when materials retain
information that could lead to the identification of the patient, including,
but not limited to:
i) A schema for
maintaining confidentiality, such as a coding system;
ii) A system for a secure audit trail from
primary cell lines to those submitted to the repository, which identifies all
individuals who have accessed the information; and
iii) A policy governing whether and how to
deliver clinically significant information to donors.
D) Establish the following standard
practices:
i) A process for assignment of a
unique identifier to each sample;
ii) A process for characterizing cell
lines;
iii) A process for
expanding, maintaining and storing cell lines;
iv) A system for quality assurance and
control;
v) A website that contains
specific descriptions and data related to the cell lines available;
vi) A procedure for reviewing applications
for cell lines;
vii) A process for
tracking disbursed cell lines and recording their status when shipped,
including number of times the stem cell line has been subcultured or
transferred;
viii) A system for
auditing compliance;
ix) A schedule
of charges;
x) A statement of
intellectual property policies;
xi)
A process to create a material transfer agreement or user agreement;
xii) A liability statement; and
xiii) A system for disposal of
material.
E) Establish
clear criteria for distribution of cell lines, including, but not limited to,
written approval of the research by the ESCRO committee or equivalent body at
the recipient institution.
k) Research Use of Stem Cell Lines
1) Once stem cell lines have been derived,
investigators and grantees shall monitor their use in research.
2) Grantees shall require documentation of
the source of all stem cell lines, including whether the cells were imported
into the institution or generated locally. The investigator's notice to the
institution shall include evidence of written IRB approval of the procurement
process, and adherence to Guidelines for Human Embryonic Stem Cell Research. In
the case of lines imported from another institution, documentation that these
criteria were met at the times of derivation will suffice.
3) Each grantee shall maintain a registry of
its investigators who are conducting stem cell research.
4) The investigators shall submit all
protocols involving the combination of embryonic stem cells with nonhuman
embryos, fetuses or adult animals to the ESCRO committee for consideration of
the consequences of the human contributions to the resulting
chimeras.
5) The ESCRO committee
shall review experiments in which embryonic stem cells, their derivatives or
other pluripotent cells are introduced into nonhuman fetuses and allowed to
develop into adult chimeras, including consideration of any major functional
contributions to the brain.
6) The
IRB shall review use of existing stem cells when the research involves
introduction of the stem cells or their derivatives into patients or the
possibility that the identity of the donors of the blastocysts, gametes or
somatic cells is readily ascertainable or might become known to the
investigator. Documentation of the IRB's review shall be included with the
grant application (see Section
995.100(c)(17)
).
l) Research involving nonhuman mammals
1) Standards for the review of research
involving nonhuman mammals shall be based on the requirements of the Animal
Welfare Act and the Public Health Service Policy on Humane Care and Use of
Laboratory Animals (see Section 995.15). All research involving nonhuman
animals shall be approved by the institution's IACUC.
2) Introduction of embryonic stem cells into
nonhuman mammalian blastocysts shall be considered by investigators and
approved by the ESCRO committee only under circumstances in which no other
experiment can provide the information needed.
3) Animal embryonic stem cells shall not be
transplanted into a human blastocyst.
4) Human embryonic stem cells shall not be
transplanted into nonhuman primates.