Stem Cell Research at the George Washington University

PART ONE: GENERAL PROVISIONS; STANDARDS AND PROCEDURES FOR REVIEW
I. / Institutional Oversight of Human Pluripotent Stem Cell Research at the George Washington University
Research involving human pluripotent stem cells (hPSCs) being conducted by GW faculty, staff or students or involving the use of GW facilities or resources is subject to oversight by the GW Institutional Stem Cell Research Oversight (ISCRO) Committee. Covered research includes:
A. / All research using human embryonic stem cells (hESCs);
B. / All research involving somatic cell nuclear transfer (SCNT) involving human cells;
C. / Other hPSCs (e.g., human induced pluripotent stem cells [iPSCs], human embryonic germ cells [hEGCs]) where the research involves:
1. / Introduction of the cells into humans;
2. / Introduction of the cells into the central nervous system of non-human primates;
3. / Introduction of the cells into non-human animals and there is a reasonable possibility of the cells giving rise to gametes; or,
4. / Creation of gametes or embryos.
II. / Purpose of the GW ISCRO Committee
The primary purpose of the GW ISCRO Committee is to provide ethical oversight for all research conducted at GW using hESCs or SCNT involving human cells, as well as for research with other hPSCs under the limited circumstances identified in Section I.C. above. The GW ISCRO Committee also requires compliance with other applicable governmental regulations and GW Institutional policies.
The GW ISCRO Committee serves as an educational resource for researchers engaged in this research. The GW ISCRO Committee also serves as a consultative body for researchers working with all types of human adult stem cells. Upon referral by the Institutional Animal Care and Use Committee (IACUC), the Institutional Biosafety Committee (IBC), or an Institutional Review Board (IRB), the GWISCRO Committee reviews research protocols that the referring committee believes would benefit from such review.
III. / The Authority of the GW ISCRO Committee
A. / Initial Approval of Human Stem Cell Research
The GW ISCRO Committee shall have the authority to approve, require modifications of, or withhold approval of all research activities that fall under its jurisdiction, (see Part One, Section I) within the GW. In addition, other Divisions of the University may refer research protocols to the GW ISCRO Committee for review.
B. / Continuing Oversight
1. / Approved research shall be reviewed by the GW ISCRO Committee every year, or more frequently, as determined by the GW ISCRO Committee on a case-by-case basis. The investigator is responsible for submitting the renewal application in a timely manner as specified by the GW ISCRO, but no later than 6 weeks prior to the expiration date. All investigators will be notified in advance of specific renewal requirements. Failure to submit the application by the deadlinemay result in withdrawal of approval.
2. / Progress Reports and Adverse Event Reports pertaining to GW ISCRO Committee approved research and submitted to a University IRB, IACUC, and/or IBC must also be submitted to the GW ISCRO Committee.
3. / No modifications to GW ISCRO Committee approved research shall be implemented prior to GW ISCRO Committee approval of the modifications, except when a deviation is necessary to prevent imminent harm. Such deviations should be reported to the GW ISCRO Committee within 3 business days. The GW ISCRO Committee has the authority to review and approve, require modifications of, or withhold approval of all proposed modifications to GW ISCRO Committee approved research prior to the implementation of such modifications.
C. / Monitoring of GW ISCRO Committee Approved Research
The GW ISCRO Committee or its representatives shall have the authority to observe the conduct of any research activity subject to GW ISCRO Committee oversight. This function includes the authority to review all records associated with the conduct of the research.
D. / Restrictions, Suspension, and Termination of Research
1. / The GW ISCRO Committee shall have the authority to place restrictions on research activities that fall under its jurisdiction. The GW ISCRO Committee will notify other relevant committees (e.g., IRB, IACUC, IBC, and Committee on Conflict of Interest [CCOI])of any such restrictions.
2. / The GW ISCRO Committee shall have the authority to suspend or terminate its approval of research that falls under its jurisdiction and that is not being performed in compliance with GW ISCRO Committee requirements, applicable governmental regulations, and/or University policies. The GW ISCRO Committee will notify the GW Institutional Official(s), as well as other relevant committees (e.g., IRB, IACUC, IBC, CCOI) of any suspension or termination.
3. / If a GW sponsor or a GW researcher participates as a co-investigator in research at a site outside the University that would be subject to GW ISCRO Committee oversight if it were conducted at GW, the GW ISCRO Committee shall have the authority to terminate the participation of GW researchers in the research if that research is not in compliance with GW ISCRO Committee requirements. In such cases, the GW ISCRO Committee will inform the responsible Institutional Official(s) at GW and the relevant official at each institution other than GW involved in the research of the termination.
E. / Review of Research within the Jurisdiction of the GW ISCRO Committee by Other University Committees or Officials
1. / Research requiring GW ISCRO Committee review ordinarily will be submitted for review and approval by the GW ISCRO Committee concurrently with submission of the research to any other GW entity (e.g., IRB, IACUC, IBC, COI) that may have responsibility for oversight of other aspects of the research.
2. / Research activities approved by the GW ISCRO Committee may be subject to further review, modification of, approval and/or disapproval by all relevant bodies, such as the GW IRBS; the GW IBC; the GW IACUC; and the GWVice President for Research. However, those committees and officials may not approve the conduct of research within the GW ISCRO Committee's jurisdiction if approval was previously withheld by the GW ISCRO Committee.
3. / The GW ISCRO Committee will make annual informational reports (e.g., number of applications reviewed, number approved, number for which approval was withheld, and number involving human subjects) to the GW IRBs.
F. / Principal Investigator Responsibilities
The GW ISCRO requires that the principal investigator (PI) of a GW ISCRO application must be a faculty member at GW. Faculty positions that may serve as a PI are Professor, Associate Professor, Assistant Professor, Instructor, Research Associate, Lecturer or Assistant. A faculty mentor should submit a protocol application as PI for research awarded (such as a Post-Doctoral Fellowship award from the Maryland Stem Cell Research Fund) to a post-doctoral fellow. In this situation, the post-doctoral fellow should be listed as a co-investigator. The PI must understand the responsibilities associated with conducting human stem cell research. PIs and co-investigators must comply with federal regulations, state and local laws, Organization policies, and the determinations of the GW ISCRO. PIs are responsible for training staff and for conducting the research at the Organization.
G. / Education and Training
All study team members engaged in research, subject to oversight by the GW ISCRO Committee shall complete educational activities related to the ethics of such research, as specified by the GW ISCRO Committee.
IV. / Conflicts of Interest - GW ISCRO Committee Chair, Members and Consultants
A. / Disclosure
GW ISCRO Committee Chair and GW ISCRO Committee members shall be required to disclose conflicts of interest at the beginning of each GW ISCRO Committee meeting. Conflicts of interest include being a listed investigator, having a financial interest in the sponsor of the research or the technology being evaluated, as defined by the GW SOM Policy on Conflict of Interest, or having any other conflict that might reasonably be perceived to inhibit a fair and unbiased review of the research.
B. / Abstention from Deliberations and Decision Making
GW ISCRO Committee members who have conflicts of interest with respect to protocols submitted for GW ISCRO Committee review will abstain from participation in GW ISCRO Committee deliberations and decisions relative to those protocols. They will not be present in the room during voting on proposals. However, such members may be consulted on the research prior to voting.
C. / Consultants and Conflict of Interest Disclosure
Consultants shall be asked, at the time they are contacted to review a research study, if they have a conflict of interest with the study on which they are being asked to consult.
V. / Prohibited Research
In accordance with prevailing ethical and policy guidance and applicable law, the following categories of research are currently prohibited at GW:
A. / Research involving the introduction of hPSCs into human blastocysts;
B. / Research involving the introduction of hPSCs into non-human primate blastocysts;
C. / Research involving in vitro culture of any intact human embryo for longer than 14 days or until formation of the primitive streak begins, whichever occurs first; and
D. / Breeding of animals that have had hPSCs introduced into the germ line.
This list may be revised to reflect changes in prevailing ethical and policy guidance and applicable law.
VI. / Standards for GW ISCRO Committee Review
In conducting review of proposed research, the GW ISCRO Committee will take into account considerations that include the following:
A. / Procurement of Gametes, Blastocysts, or Somatic Cells for hPSC Generation
For the purposes of GW ISCRO Committee review, donors of human materials will be considered human research subjects (per 45 CFR 46), regardless of the context in which the materials are procured. The oversight of the procurement process, including provisions for informed consent, is under the purview of a properly constituted IRB. Nevertheless, information about the process will be considered by the GW ISCRO in its deliberations.
The ethical and legal issues related to hPSC research depend in part on the context in which human materials are procured (e.g., infertility treatment, research, clinical care). The context of procurement will involve established standards of care that will be taken into consideration during GW ISCRO Committee deliberations. Therefore, protocols must describe:
1. / Ethical considerations for procurement of human materials in the context of clinical care:
a. / Plans to ensure that an individual's decision about donation will not affect the quality of care s/he receives;
b. / Plans to ensure that infertility treatment teams will not generate more oocytes than clinically necessary;
c. / In the case of hPSCs derived from fetal tissue, plans to ensure that an individual's decision about donation is separate from the decision to terminate the pregnancy.
2. / Voluntariness of Consent
a. / Plans to ensure that undue inducements will not be provided for donation (e.g., financial or special considerations for services);
b. / Plans to ensure that decisions to donate are made free from undue influence (e.g., the investigator and the attending physician responsible for the infertility treatment are not the same person).
The IRBs may be consulted if either of the above (VI, A, 2.a or 2.b) is in question.
3. / Informed Consent:
In addition to the required elements of informed consent specified in 45 CFR 46. 116, the informed consent process and document must disclose the following, if applicable:
a. / That procured human materials will be used to derive hPSCs for research that may include research on human transplantation;
b. / That embryos will be destroyed in the process of deriving hPSCs;
c. / That embryos will not be used to produce a pregnancy and will not be allowed to develop in culture for longer than 14 days from fertilization;
d. / That procured human materials might involve:
i. / The introduction of the cells into humans,
ii. / The introduction of the cells into the central nervous system of non-human primates,
iii. / The introduction of the cells into non-human animals and there is a significant possibility of the cells giving rise to gametes, or
iv. / The creation of gametes or embryos;
e. / That resulting cell lines will be genetically similar or identical to the donor;
f. / That the hPSCs and/or cell lines might be used in research involving genetic manipulation of the cells or the mixing of human and non-human cells in animal models;
g. / That derived hPSCs and/or cell lines might be kept for many years;
h. / Whether the donated material will be coded or deidentified prior to research use
i. / If donors' identities are retained (even if coded), whether donors can elect to be contacted to receive information obtained through studies of the cell lines;
j. / That restricted and/or directed donation (e.g., to individuals or groups) are/is not permitted;
k. / That the results of study of the hPSCs may have commercial potential and that the investigator and institution may benefit; however, the donor will not receive financial or any other benefits from any commercial development;
l. / That the research is not intended to provide direct medical benefit to the donor(s);
m. / That neither consenting nor refusing to donate embryos for research will affect the quality of any care provided to potential donors;
n. / Risks to donors.
B. / Transfer of Human Materials from Outside Entities
To determine the scientific and ethical integrity of hPSC research under its purview, the GW ISCRO Committee must examine the circumstances under which human materials were (or will be) procured for use in such research and the details of the derivation of cell lines. The applications must include documentation of the provenance of all hPSC lines, whether the cell lines were imported into the Institution or derived locally. Such documentation must include evidence of IRB-approval of the procurement process, evidence of and adherence to basic ethical and legal principles of procurement, and compliance with applicable laws.
C. / Derivation of hESCs
Protocols must describe:
1. / Appropriate expertise of the research team in the derivation or culture of either human or non-human ESCs;
2. / The scientific rationale for the need to generate new hESCs, as well as the basis for the number of blastocysts used in the derivation process;
3. / Any plans for compliance with an established set of good manufacturing practices (GMPs), and if so, with which GMPs;
4. / How any new hESC lines will be characterized, validated, stored, and distributed.
D. / Transfer of hPSCs into Non-human Primates
Protocols must describe:
1. / Why hPSCs are required in lieu of stem cells from non-human primates or other animals;
2. / Relevant animal work that precedes the proposed work;
3. / Quality control of the cell lines and their derivatives, (such as genetic stability, freedom from contamination);
4. / The developmental stage of the non-human animal to which the cells will be transferred;
5. / The procedures that will be used to assess whether the animal may acquire cognitive characteristics that are thought of as distinctly human, as well as how non-human primates will be evaluated (pre- and post-transplant).
E. / Trials with Humans
Protocols must describe:
1. / Pre-clinical testing with animal models;
2. / Quality control of hPSC lines and their derivatives;
3. / Selection of subjects (e.g., the appropriateness of using healthy volunteers in early human trials);
4. / Risk of infectious disease (e.g., from cells cultured in mouse feeder layers);
5. / Risk of transfer of genetic disorders;
6. / Risks of misdifferentiation, mistargeting, tumor formation, and immune rejection;
7. / Risk of uncontrolled cell growth.
F. / Privacy
Although IRBs and other bodies have jurisdiction over the confidentiality of the identifying information of human research subjects, there may be cases in which identifying information is transmitted with hPSC lines for research that does not fall under the jurisdiction of any of these groups. Therefore, whenever hPSC research under GW ISCRO jurisdictioninvolves the transmission of identifying information on donors of gametes, blastocysts, hPSC lines or somatic cells, protocols must describe the information to be obtained and the steps taken to ensure that the privacy of donors is protected, (e.g., how the requirements of HIPAA will be met).
G. / Justice
Protocols must describe mechanisms established for subject selection. The process for selection among groups and individuals to participate must be equitable.
H. / Collaboration with Other Institutions
Where GW faculty, staff or students acting in their capacity as GW faculty, staff or students respectively, collaborate with a researcher at another institution, protocols must describe the oversight and review mechanisms at the other institution.
VII. / Procedures for Research Requiring GW ISCRO Committee Review
The review process and the records of the GW ISCRO Committee will be maintained as confidential to the extent permitted by law.
A. / Quorum Requirements
The GW ISCRO Committee shall officially conduct its review of proposed research at convened meetings at which at least fifty percent (50%) of the voting members (i.e., a quorum) of the GW ISCRO Committee are present, in person or by electronic conferencing. Quorum requirements also include that there be representation of at least two scientific members and one member whose expertise is in ethical issues. The Chair may appoint a designee to act as Chair, in the event neither is available for a convened meeting.
B. / GW ISCRO Committee Review of Research Proposals
1. / Each research study requiring review and approval by the convened GW ISCRO Committee shall be addressed separately at GW ISCRO Committee meetings.
2. / Submitted protocols will be made available to GW ISCRO Committee members in advance of GW ISCRO Committee meetings to allow sufficient time for review.
3. / The primary reviewers for each protocol shall summarize the proposed research followed by an open discussion of the research by the GW ISCRO Committee members.
4. / The reviewers may contact the principal investigator with questions about the submitted protocol. In such cases, the principal investigator will have an opportunity to submit revisions before full GW ISCRO Committee review.
5. / Reviewers who are absent from a full GW ISCRO Committee meeting may provide written comments regarding the proposed research, but absent members shall not be counted in the GW ISCRO Committee vote.
6. / Following open discussion, the GW ISCRO Committee co-chair or a designeeshall call for a vote of the GW ISCRO Committee to grant:
a. / Full Approval: No changes are required to the proposed research;
b. / Approval Pending Concurrence with GW ISCRO Committee-directed Changes: The proposed research may be granted full approval by the GW ISCRO Committee Chair pending principal investigator concurrence with specific revisions stipulated by the GW ISCRO Committee. The research may not receive full approval until such time that the research procedures have been modified to comply with the specific revisions stipulated by the GW ISCRO Committee and such revisions have been reviewed and approved by the GW ISCRO Committee co-chair ora designee;