Human Embryonic Stem Cell Research Guidelines

Effective: February 28, 2008

Policy Statement

Washington University (WU) is committed to maintaining the highest ethical standards in our community and our professions, and complying with relevant laws and regulations. The University also expects investigators to commit to the ethical and responsible conduct of research, the protection of human subjects and the appropriate stewardship of sponsored funds.

Washington University publishes these guidelines to support investigators engaged in human embryonic stem cell research, assure the responsible conduct of human embryonic stem cell research and comply with federal, state and local laws and regulations.

These Guidelines are based on the National Academy of Science report, Guidelines for Human Embryonic Stem Cell Research, (2005).

For more information on the roles and responsibilities of investigators conducting research at Washington University (WU), please see the University Code of Conduct (http://codeofconduct.wustl.edu/) and the Research Roles and Responsibilities (http://roles.wustl.edu/).

Guidelines

1. Institutional Oversight

   In order to provide appropriate oversight of human embryonic stem cell research, Washington University has established the Embryonic Stem Cell Research Oversight committee (ESCRO). The ESCRO, reporting to the Vice Chancellor for Research, is responsible for the following:

   1. Provide scientific and ethical review of all WU research projects involving human embryonic stem cells;
   2. Provide oversight regarding issues related to derivation and use of human embryonic stem cell lines;
   3. Review all new and continuing WU research projects involving human embryonic stem cells at least annually for compliance with applicable regulatory requirements and WU policies, including these guidelines;
   4. Maintain a registry of human embryonic stem cell research conducted at WU or by WU investigators;
   5. Ensure documentation of the provenance of human embryonic stem cell lines including evidence of IRB review and approval as well as approval of the procurement process;
   6. Monitor national, state, and local ethical, regulatory and policy discussions and make recommendations to modify the WU policy as needed;
   7. Educate investigators on the ethical, legal, and policy issues in human embryonic stem cell research; and
   8. Assist investigators in assessing which regulations or types of review might apply to proposed research activities.

   ESCRO members will be appointed by the Vice Chancellor of Research in consultation with the Executive Vice Chancellor/Dean of the School of Medicine. The membership of this committee should reflect the scientific, medical and ethical expertise necessary to perform the above responsibilities.

   The ESCRO membership must include a faculty representative experienced in conducting research involving human subjects and a representative of the public. Additional members may be appointed who are qualified to address the following areas:

   • Developmental biology
   • Stem cell research
   • Molecular biology
   • Assisted reproduction
   • Medical ethics or legal issues

2. Other Institutional Oversight

   In addition to the scientific and ethical reviews performed by the ESCRO, the oversight and guidance of the IRB is required in many cases.

   1. WU requires IRB review and approval for all human embryonic stem cell research that use human embryonic stem cell preparations. Both ESCRO and IRB review and approval are required in order to conduct research using human embryonic stem cells.

      1. Research involving pre-existing anonymous human embryonic stem cell lines is regarded as non-human research but must be reported to and reviewed by the ESCRO. Such research must also be submitted to the IRB to confirm and document the non-human determination provided. Any questions about the status of non-living human research must be referred to the IRB which is solely responsible for such determinations.

      2. Appropriate documentation of the provenance of the cell lines (including evidence that the procurement process was approved by an IRB, to ensure adherence to the basic ethical and legal principles of informed consent and protection of confidentiality) and evidence of compliance with any required compliance reviews must be provided. (See Section VII for other applicable, compliance policies.)

      3. Research involving the procurement of pre-existing cell lines in which identifiable information is available must be reviewed by the IRB.

      4. Research involving the donation or procurement of blastocysts, gametes, or somatic cells requires IRB review. (See Section IV).

   2. Appropriate review and approval by other WU compliance committees prior to IRB review may be required. Section VII provides more information about these potential types of review.

   3. The IRB may require investigators or other members of the research team to complete educational programs including but not limited to the WU mandatory human subjects research program or programs in Good Tissue Practice.

3. ESCRO Scientific and Ethical Review of Proposed Research

   The ESCRO will divide research proposals into four categories that will be used to set limits on the types of research conducted at WU and determine the appropriate level of oversight. These four categories are:

   1. Research that is permissible after notification of the ESCRO committee and completion of the reviews mandated by current requirements.

      1. Research that is purely in vitro human embryonic stem cell research using pre-existing coded or anonymous human embryonic stem cell lines is generally permissible provided that notice of the research, documentation of the provenance of the cell lines and evidence of compliance with any of the required or mandated compliance committee reviews is provided to the ESCRO committee. This includes appropriate review, determinations and approvals by the IRB.

   2. Research that is permissible only after review and approval by the ESCRO.

      1. The ESCRO must review and approve all research proposals that involve an attempt to derive new human embryonic stem cell lines.

         The scientific rationale for the need to generate new human embryonic stem cell lines, by whatever means, should be clearly presented, and the basis for the numbers of blastocysts or oocytes needed should be justified. Such requests should be accompanied by evidence of the appropriate IRB approval of the derivation process or the procurement of blastocysts, gametes or somatic cells (See Section IV).

      2. The ESCRO must review and approve all research proposals involving the introduction of human embryonic stem cells or any products derived from human embryonic stem cells into non-human animals. Particular attention will be paid to the probable pattern and effects of differentiation and integration of the human cells into the nonhuman tissues.

      3. The ESCRO must review and approve all research proposals involving the introduction of human embryonic stem cells into murine blastocysts including the generation of chimeric mice.

      4. The ESCRO must review and approve all research proposals in which personally identifiable information about the donors of the blastocysts, gametes or somatic cells from which the human embryonic stem cells were derived is readily ascertainable by the investigator.

   3. The ESCRO will not approve the following types of research at this time:

      1. Research involving human embryonic stem cells derived from blastocysts obtained from IVF that was performed for research purposes only;
      2. Research involving in vitro culture of any intact human blastocyst, regardless of derivation method, for longer than 14 days or until formation of the primitive streak begins, whichever occurs first;
      3. Research involving the introduction of embryonic stem cells obtained from any species (including humans) into human blastocysts.

   4. Research that is not permitted.

      1. Transfer of products of somatic cell nuclear transfer (SCNT) into the human uterus, including research on cloning to have children.
      2. Transfer of human blastocysts containing embryonic stem cells into the uterus of any non-human species.
      3. a. Breeding of animals in which human embryonic stem cells have been introduced at any stage of development.

      In addition to the scientific and ethical review, the ESCRO committee will review the research proposal for compliance with other regulations or policies including the human embryonic stem cell Financial and Costing Policies. (See Section VIII.)

4. Procurement of Gametes, Blastocysts or Cells for Human Embryonic Stem Cell Generation

   IRB review, approval and monitoring is required for the procurement process used to obtain donated blastocysts in excess of clinical need after infertility treatment. Similarly, IRB review and approval is required to obtain oocytes, sperm, and somatic cells donated for development of human embryonic stem cell lines derived through SCNT. Informed consent must be obtained from any person whose somatic cells, gametes or blastocysts are used in human embryonic stem cell research. In addition, the IRB will review research protocols for compliance with the Health Insurance Portability and Accountability Act (HIPAA) and other applicable federal and state laws and regulations.

   For more specific guidance from the IRB regarding the consent process, please see the IRB website at http://hrpo.wustl.edu

   The items outlined below are considerations to be used in the development of any protocol.

   • Obtain consent from each donor at the time of donation or thereafter.
   • Blastocysts resulting from the IVF process may not be used without the consent of both gamete donors and consent should be obtained at the time of donation or thereafter.

   • No person may purchase or sell human eggs, sperm or blastocysts for stem cell research purposes.

     Women who undergo hormonal induction to generate oocytes specifically for research purposes (such as SCNT) ***should be reasonably reimbursed only for their direct expenses, time and inconvenience incurred as a result of the procedure, as reviewed and approved by the IRB.

   • The attending physician or embryologist responsible for the infertility treatment and the investigator deriving or proposing to use human embryonic stem cells from that patient should not be the same person. The attending physician and embryologist must be blinded to decisions about the use of excess blastocysts for research.

5. Adherence to Standards of Clinical Care

   WU has already established certain standards for the clinical care of patients, subjects and health professionals involved the donation and consent process. These standards are designed to ensure that every donor has a physician whose primary responsibility is caring for the donor. The following standards are in addition to the appropriate standards of care already in place:

   • Staff with ethical issues related to human embryonic stem cell research may not be forced to participate in oocyte retrieval or the consent process but may not deny care of donor or recipient before or after the procedure; and
   • Treatment decisions must be unaffected by the donation decision.

6. Standards for Investigators Who Wish to Bank Cell Lines

   WU anticipates investigators may want to bank human embryonic stem cell lines. There are currently no plans for an institutional approach to cell line banking. Investigators must follow these standards when establishing and maintaining a cell line bank:

   • Obtain IRB review and approval, including appropriate informed consent for the banking of cell lines;
   • Maintain appropriate records;
   • Protect donor privacy;
   • Develop tracking and distribution guidelines and systems;
   • Cell lines that are shipped into the University must have a Material Transfer Agreement approved by the Office of Technology Management (OTM), must be registered with the ESCRO and all documentation required by the ESCRO must be provided;
   • Cell lines that are shipped out of the University must have a Material Transfer Agreement approved by the OTM and must be shipped according to University policy;
   • All members of the research team must be appropriately trained in these standards, and
   • The Office of the Vice Chancellor reserves the right to monitor cell banks for compliance with this and other policies, guidelines and regulatory standards.

7. Other Applicable WU Policies

   Investigators should be aware that the review and approval by the ESCRO or the IRB is in addition to other University policies, federal regulations and state and local laws governing research. Other policies that may need to be considered include but are not limited to:

   • Animal Studies Committee http://medicine.wustl.edu/asc
   • Conflict of Interest http://medcoi.wustl.edu/
   • HIPAA http://hipaa.wustl.edu/
   • Human Research Protection Office http://hrpo.wustl.edu
   • Material Transfer Agreements http://otm.wustl.edu/mainlinks/materialtransfer.html
   • Institutional Biological and Chemical Safety Committee
     • Recombinant DNA http://www.ehs.wustl.edu/new/rdna.htm
   • Radiation Safety http://radsafety.wustl.edu/
   • Other research policies http://research.wustl.edu

   In addition, certain types of research may be subject to other regulations such as those promulgated by the FDA.

8. Financial and Costing Policies

   On August 9, 2001, President Bush announced that federal funds may not be used for research using human embryonic stem cell lines unless:

   1. The stem cells were derived from a blastocyst that was created for reproductive purposes and was no longer needed;
   2. Informed consent was obtained for the donation of the blastocyst, and the donation did not involve financial inducements; and
   3. The process of derivation was begun prior to 9 pm EDT on August 9, 2001.

   The National Institutes of Health (NIH) has established a registry of the stem cell lines that satisfy these criteria ("registry lines") making research on these lines eligible for federal funding. The registry is available at http://stemcells.nih.gov/research/registry/eligibilityCriteria.asp. Research on human embryonic stem cell lines not listed on the NIH registry is ineligible for federal funding.

   Although the August 9, 2001 policy bars the use of federal funds for ineligible human embryonic stem cell research, it does not prevent researchers from conducting such research with non-federal funds. To comply with the August 9, 2001 policy, researchers and institutions that receive federal funding must keep separate accounts of the expenses associated with ineligible human embryonic stem cell research to ensure that no federal funds are used, directly or indirectly, to support such research. According to the NIH, institutions will satisfy that requirement if they treat the costs of ineligible human embryonic stem cell research as "unallowable" costs and follow applicable federal cost principles included in OMB Circular A-21. See NIH, Stem Cell Information, Frequently Asked Questions (NIH FAQs), available at http://stemcells.nih.gov/info/faqs.asp.

   The following WU guidelines, based on the cost principles outlined in A-21 and on guidance provided by the DHHS Division of Cost Allocation, provide essential information about the financial compliance requirements for investigators who plan to conduct human embryonic stem cell research. For more specific information on the financial policies, visit the Sponsored Projects Accounting (SPA) website at http://spa.wustl.edu/.

   Proposal Budget Preparation

   All human embryonic stem cell research proposals must include a budget that will be reviewed and approved by the School of Medicine Grants and Contracts Office or the Danforth Research Office. This review will assess the appropriate budgeting of direct costs.

   Direct and F&A Costs

   • The direct costs of human embryonic stem cell research that are eligible for federal funding must be charged to the appropriate federal sources of funding and accumulated in a separate account.
   • The direct costs of human embryonic stem cell research that are ineligible for federal funding must be charged only to non-federal sources of funding and accumulated in a separate account.
   • Normally the same laboratory may not be used for both federally funded and non-federally funded research. Decisions about the use of laboratory space must be made in conjunction with the appropriate Dean.
   • Investigators and their staffs must separate eligible and ineligible activities in such a way that assures that costs incurred in the research are charged consistently to the appropriate funding source.
   • Federal regulations forbid the shifting of costs from ineligible research activities to federally sponsored activities.
   • During preparation of federal F&A cost proposals, the University will strictly adhere to A-21 principles regarding the allocation of F&A costs to both federally sponsored and other activities, which would include ineligible human embryonic stem cell research. The costs of ineligible human embryonic stem cell research should be included in the regular F&A cost allocation base and associated indirect costs must be allocated pursuant to ordinary allocation principles.

9. Applicability

   The University guidelines governing human embryonic stem cell research apply to all investigators, regardless of funding source. Awards will be established only after appropriate compliance is documented.

10. Approvals

    This policy was approved by the Executive Committee on Research on February 28, 2008.

    Original Policy Date: December 18, 2001
    Previously Revised: November 21, 2005