Sara Bible, Dean of Research Office Stanford University

1. ©National Council of University Research Administrators FRAIX 2008 Sara Bible, Dean of Research OfficeStanford University Stem Cell Research: Forging Ahead Without Federal Funds Welcome to the tutorial on Human Embryonic Stem Cell Research Special Operating Procedures. I’m Patti McCabe, your on-line instructor. This tutorial will help to familiarize you with Stanford’s Special Operating Procedures for Human Embryonic Stem Cell Research.  Private donors, the State of California, and many sponsors including the federal government have made funds available for this research.  A major concern for the Stanford community is the administrative details about how to carry out this research in compliance with legislative and other governmental requirements. To address this, Stanford has developed Special Operating Procedures. These Procedures in combination with Stanford’s existing policies and procedures will ensure compliance. Welcome to the tutorial on Human Embryonic Stem Cell Research Special Operating Procedures. I’m Patti McCabe, your on-line instructor. This tutorial will help to familiarize you with Stanford’s Special Operating Procedures for Human Embryonic Stem Cell Research.  Private donors, the State of California, and many sponsors including the federal government have made funds available for this research.  A major concern for the Stanford community is the administrative details about how to carry out this research in compliance with legislative and other governmental requirements. To address this, Stanford has developed Special Operating Procedures. These Procedures in combination with Stanford’s existing policies and procedures will ensure compliance.

2. ©National Council of University Research Administrators FRAIX 2008 About This Tutorial Intended Audience This tutorial is intended for Stanford personnel, including faculty, staff, postdoctoral scholars, and students, as well as visiting scholars and other researchers, who will be working on research projects involving human embryonic stem cells. Required Training All personnel must complete this tutorial satisfactorily as a prerequisite to beginning work or study associated with human embryonic stem cells. It is the PI’s responsibility to ensure that personnel complete both tutorials. This tutorial includes a post test that must be completed with 100% accuracy. You may take the post test now if you believe you know all the information in this tutorial. Project Task Award (PTA) A Project Task Award (account) can be opened once the PI has completed the tutorials and the SCRT form. Tutorial Topics Impact of federal funding issues on administration of hESC research Stanford’s Human Embryonic Stem Cell Research Special Operating Procedures for: material transfer agreements accounting (PTA) effort allocation and certification facilities equipment expendable materials and supplies derivatives research data and intellectual property Using the SCRT Form This tutorial reviews the specific actions required for administration of human embryonic stem cell research outlined in the Procedures. Please read the tutorial topics listed on the slide now. This tutorial must be completed by University personnel, including faculty, staff, postdoctoral scholars, and students, as well as visiting scholars and other researchers, who will be working on projects involving human embryonic stem cells. Both the tutorial and posttest must be completed before beginning work. Note the requirements for opening a PTA listed on the right side of the slide.This tutorial reviews the specific actions required for administration of human embryonic stem cell research outlined in the Procedures. Please read the tutorial topics listed on the slide now. This tutorial must be completed by University personnel, including faculty, staff, postdoctoral scholars, and students, as well as visiting scholars and other researchers, who will be working on projects involving human embryonic stem cells. Both the tutorial and posttest must be completed before beginning work. Note the requirements for opening a PTA listed on the right side of the slide.

3. ©National Council of University Research Administrators FRAIX 2008 Terms and Acronyms Used In This Tutorial Human Adult Stem Cells A stem cell is a master cell that can create the more specialized cells in a human. Human Embryonic Stem Cells (hESC) Human embryonic stem cells are pluripotent cells that are self-replicating, derived from human embryos and are capable of developing into cells and tissues of the three primary germ layers. Although human embryonic stem cells may be derived from embryos, such stem cells are not themselves embryos. Registered hESC Those included on the NIH Human Embryonic Stem Cell Registry. Non-registered hESC Those excluded from the NIH Human Embryonic Stem Cell Registry . hESC lines A population of identical cells that all originated from a single blastocyst. Because cell lines multiply, scientists can grow the cells for their own research and to share with colleagues. Stem Cell Research Tracking Form (SCRT) Tracking Form A internal form used at Stanford to expedite implementation of the Special Procedures for hESC research. Take a moment to familiarize yourself with the terms and acronyms used throughout this tutorial. Please note the abbreviation h-E-S-C, which we will pronounce as hESC. It is an acronym for human embryonic stem cell.Take a moment to familiarize yourself with the terms and acronyms used throughout this tutorial. Please note the abbreviation h-E-S-C, which we will pronounce as hESC. It is an acronym for human embryonic stem cell.

4. ©National Council of University Research Administrators FRAIX 2008 Background: Criteria for Federal Funding for hESC Research Federal Announcement On August 9, 2001, President George W. Bush announced that federal funds can be used for research using hESC only if they meet the following criteria. Criteria The stem cells were derived from an embryo that was created for reproductive purposes and was no longer needed; informed consent was obtained for the donation of the embryo, and the donation did not involve financial inducements; and the process of derivation was begun prior to 9 pm EDT on August 9, 2001.

5. ©National Council of University Research Administrators FRAIX 2008 Federal Announcement Impacts Federal Funding for hESC Research Because of President Bush’s announcement, Stanford has categorized hESC lines as: 1. Registered hESC LinesFederal funds may be used ONLY for research using registered hESC lines. Registered hESC lines are those included on the NIH Human Embryonic Stem Cell Registry which confirms that the stem cell lines are in compliance with the President’s criteria as stated on August 9, 2001.    2. Non-registered hESC LinesFederal funds may not be used directly or indirectly for research using non-registered hESC lines (or their derivatives). Non-registered hESC lines are excluded from the NIH registry because they do not meet federal criteria. hESC Research Can Proceed Although the August 9, 2001 announcement bars the use of federal funds for research on non-registered hESC lines, it does not prevent investigators from conducting such research with non-federal funds. On August 9, 2001, President George W. Bush announced that federal funds cannot be used for research using human embryonic stem cell lines unless they meet specific criteria. The criteria are listed in the first paragraph on the side. Please read those criteria now. hESC that meet the President’s criteria are listed on the NIH registry. Stanford refers to them as “registered” hESC lines. Federal funds may be used for research using registered hESC lines (and their derivatives). hESC lines that do not meet the President’s criteria are excluded from the registry. We refer to them as “non-registered” hESC lines. The federal government will not fund, directly or indirectly, research using non-registered hESC lines. Although the August 9, 2001 directive bars the use of federal funds for research on non-registered hESC lines, it does not prevent investigators from conducting research with non-federal funds such as gifts, departmental research, university research and non-federal sponsored projects. On August 9, 2001, President George W. Bush announced that federal funds cannot be used for research using human embryonic stem cell lines unless they meet specific criteria. The criteria are listed in the first paragraph on the side. Please read those criteria now. hESC that meet the President’s criteria are listed on the NIH registry. Stanford refers to them as “registered” hESC lines. Federal funds may be used for research using registered hESC lines (and their derivatives). hESC lines that do not meet the President’s criteria are excluded from the registry. We refer to them as “non-registered” hESC lines. The federal government will not fund, directly or indirectly, research using non-registered hESC lines. Although the August 9, 2001 directive bars the use of federal funds for research on non-registered hESC lines, it does not prevent investigators from conducting research with non-federal funds such as gifts, departmental research, university research and non-federal sponsored projects.

6. ©National Council of University Research Administrators FRAIX 2008 Your Role Implement the Procedures: to ensure hESC research can proceed unimpeded, to ensure compliance with Stanford, federal and state policies, laws and regulations, and to ensure federal funds are not used to support non-registered hESC research directly or indirectly. to ensure all faculty, staff, postdoctoral scholars, and students as well as visiting scholars and other researchers involved in hESC are trained. Each of us is responsible for implementing the Special Operating Procedures. Review the reasons we implement the Procedures listed on the slide.Each of us is responsible for implementing the Special Operating Procedures. Review the reasons we implement the Procedures listed on the slide.

7. ©National Council of University Research Administrators FRAIX 2008 Additional Responsibilities Responsibilities of Research Personnel Complete the hESC Tutorial Complete the SCRT Form for research on all hESC. Complete a Material Transfer Agreement Routing Form for each hESC line requested. Open new Project Task Award (PTA) for each research activity. Stanford’s Special Operating Procedures discuss specific additional responsibilities that cognizant office personnel and research personnel must take to ensure compliance. Please read the responsibilities listed on the slide.Stanford’s Special Operating Procedures discuss specific additional responsibilities that cognizant office personnel and research personnel must take to ensure compliance. Please read the responsibilities listed on the slide.

8. ©National Council of University Research Administrators FRAIX 2008 Costing Procedures: Introduction The following costing procedures provide guidance to ensure that federal funds are not used to support non-registered hESC research. Remember the costing procedures for hESC research are in addition to existing Stanford Policy & procedures.

9. ©National Council of University Research Administrators FRAIX 2008 SCRT Form The Stem Cell Research Tracking (SCRT) Form The form must be completed for all research that involves the use of all Human Stem Cells registered and non-registered hESC or human embryos regardless of funding source - gifts, departmental funds, university research or externally funded grants and contracts. When Must the Form Be Completed? 1. At the time of proposal (for an externally - funded project). 2. Thirty days prior to the anticipated start date (for a gift, department or university research funded project). Whenever there is a change in project location or space usage such as room additions or deletions. The Purpose of the Form Inform and seek approval from cognizant personnel. Begin the Stem Cell Oversight Committee (SCRO) review of scientific and ethical issues Alert PMO & your DPA so they can assess ownership of the equipment to be used in research. Initiate accounting – to open a Project Task Award (PTA). The SCRT Form must be completed to ensure that Stanford University is aware of all human stem cell research and other research on embryos, proposed by and awarded, or donated to University faculty. The form must be completed for all research that involves the use of registered hESC, as well as non-registered hESC, regardless of whether the funding source is: gifts, departmental funds, university research funds, or externally funded grants or contracts. Please read the slide for specific information about when the form must be completed and its purpose.The SCRT Form must be completed to ensure that Stanford University is aware of all human stem cell research and other research on embryos, proposed by and awarded, or donated to University faculty. The form must be completed for all research that involves the use of registered hESC, as well as non-registered hESC, regardless of whether the funding source is: gifts, departmental funds, university research funds, or externally funded grants or contracts. Please read the slide for specific information about when the form must be completed and its purpose.

10. ©National Council of University Research Administrators FRAIX 2008 Accounting New PTA Required Open a new Project Task Award (PTA) for each project utilizing non-registered human embryonic stem cells, whether it is gift, departmental university, or externally funded research. Open a new project-task-award referred to as a PTA, for each project utilizing non-registered hESC, whether it is gift, departmentally, university, or externally funded research.Open a new project-task-award referred to as a PTA, for each project utilizing non-registered hESC, whether it is gift, departmentally, university, or externally funded research.

11. ©National Council of University Research Administrators FRAIX 2008 Effort Allocation and Certification Follow the Special Operating Procedures for additional work involving hESC research for postdoctoral fellows and students funded 100% by federal sources. Postdoctoral fellows and students who are funded by federal institutional training grants or fellowships, such as National Research Service Awards (NRSA) are required to pursue their research training full time under the terms of the award. However, they may be permitted under the sponsor’s policy to engage in limited or part-time work beyond their federal commitments. Any such additional work must be compensated as part time employment and must be incidental to the training program. It is extremely important to follow Stanford’s established policies for allocating effort to ensure that non-registered hESC research is not supported by federal funds. As usual, effort must be confirmed through monthly review and quarterly certification of expenditure statements. If you would like to review the policy and resources for effort allocation and certification, please pause the slide, open the links and read the information. When research is funded by gift or departmental accounts, salary must be allocated and charged commensurate with effort put forth on the project! When postdoctoral fellows and students funded 100% by federal sources want to engage in limited or part-time work beyond their federal commitments in research using non-registered hESC, the work must not exceed 8 hours per week and must be incidental to the training program.It is extremely important to follow Stanford’s established policies for allocating effort to ensure that non-registered hESC research is not supported by federal funds. As usual, effort must be confirmed through monthly review and quarterly certification of expenditure statements. If you would like to review the policy and resources for effort allocation and certification, please pause the slide, open the links and read the information. When research is funded by gift or departmental accounts, salary must be allocated and charged commensurate with effort put forth on the project! When postdoctoral fellows and students funded 100% by federal sources want to engage in limited or part-time work beyond their federal commitments in research using non-registered hESC, the work must not exceed 8 hours per week and must be incidental to the training program.

12. ©National Council of University Research Administrators FRAIX 2008 Use of Stanford and Federal Facilities Federal facilities, such as the Veterans Administration Hospital and the Stanford Linear Accelerator Center, may not be used in the conduct of non-registered hESC research. In the School of Medicine the following rooms cannot be used for Non-Registered hESC: RAF-1, Biosafety Level 3 lab (BSL-3) Falk Rooms CV085, CV087, CV089, CV091, CV093A, CV095, CV095A Boswell Fish Facility 07-305-Grnd (currently under construction) DLAM Satellite Compound 1 DLAM Satellite Compound 2 Federal facilities, such as the Veterans Administration Hospital and the Stanford Linear Accelerator Center, may not be used in the conduct of non-registered hESC research. Please review the slide for specific rooms in the School of Medicine, which CANNOT be used to perform non-registered hESC research.Federal facilities, such as the Veterans Administration Hospital and the Stanford Linear Accelerator Center, may not be used in the conduct of non-registered hESC research. Please review the slide for specific rooms in the School of Medicine, which CANNOT be used to perform non-registered hESC research.

13. ©National Council of University Research Administrators FRAIX 2008 Facilities for Non-registered hESC Research Where research on non-registered hESC is conducted Use the SCRT Form to list each lab, room, and office. This will alert your DPA and the PMO to locate and identify all equipment that will be used. This will also alert CMA to research the funding of each facility for any federal contribution. Route the SCRT form to the Research Management Group or your Institutional Representative. Update and re-route the form before the project location changes. Where research on non-registered hESC is conducted: use the SCRT Form to list each lab, room, and office where non-registered hESC research will take place. Don’t forget to list ancillary room and locations where items such as freezers are located. The SCRT Form will serve as notification to your Department Property Administrator and the Property Management Office to locate and tag all equipment in the space. The Cost and Management Analysis Group will also use the information to research the funding of each facility for any federal contribution. Route the SCRT form to the Research Management Group or your Institutional Representative. Update and re-route the form whenever the project location changes.Where research on non-registered hESC is conducted: use the SCRT Form to list each lab, room, and office where non-registered hESC research will take place. Don’t forget to list ancillary room and locations where items such as freezers are located. The SCRT Form will serve as notification to your Department Property Administrator and the Property Management Office to locate and tag all equipment in the space. The Cost and Management Analysis Group will also use the information to research the funding of each facility for any federal contribution. Route the SCRT form to the Research Management Group or your Institutional Representative. Update and re-route the form whenever the project location changes.

14. ©National Council of University Research Administrators FRAIX 2008 Space Inventory Coding Use established inventory procedures to code all hESC research in the iSpace system. Code space as organized research or departmental research, depending on the funding of the research. Use the Research Explanation field of the ispace system to document non-registered hESC research Review the Stanford University Space Inventory Instructions for in depth guidance If you are responsible for space inventory, follow the established space inventory instructions to code all hESC research. The links on the slide provide instructions.If you are responsible for space inventory, follow the established space inventory instructions to code all hESC research. The links on the slide provide instructions.

15. ©National Council of University Research Administrators FRAIX 2008 Equipment Approval In a facility where non-registered hESC research is performed, all equipment, including equipment in your current inventory and equipment that is subsequently purchased regardless of funding source, must be reviewed by the Property Management Office to determine if it can be used in non-registered hESC research. It will be tagged as either "Approved for Use on Non-registered hESC", or, "Do Not Use on Non-registered hESC “. Please read the tagging process discussed on the slide.In a facility where non-registered hESC research is performed, all equipment, including equipment in your current inventory and equipment that is subsequently purchased regardless of funding source, must be reviewed by the Property Management Office to determine if it can be used in non-registered hESC research. It will be tagged as either "Approved for Use on Non-registered hESC", or, "Do Not Use on Non-registered hESC “. Please read the tagging process discussed on the slide.

16. ©National Council of University Research Administrators FRAIX 2008 Equipment Ownership Categories Ownership and use restrictions determine whether equipment can be used. Equipment ownership will fall into one of three categories: equipment purchased and owned by the federal government, equipment purchased with federal funds but owned by Stanford, and equipment purchased and owned by Stanford. The Property Management Office will research ownership, determine if equipment can be used, and give approval whenever possible. Once equipment is reviewed it will be tagged. All equipment located in a space where non-registered hESC research is conducted must be tagged. The Department Property Administrator is responsible for tagging the equipment. Equipment owned by the federal government cannot be used, and must be tagged "Do Not Use on Non-registered hESC“. Equipment owned by Stanford can be used, and must be tagged "Approved for Use on Non-registered hESC“. Equipment purchased with federal funds and owned by Stanford may be used if it meets one of two criteria. Please read the criteria on the slide.Ownership and use restrictions determine whether equipment can be used. Equipment ownership will fall into one of three categories: equipment purchased and owned by the federal government, equipment purchased with federal funds but owned by Stanford, and equipment purchased and owned by Stanford. The Property Management Office will research ownership, determine if equipment can be used, and give approval whenever possible. Once equipment is reviewed it will be tagged. All equipment located in a space where non-registered hESC research is conducted must be tagged. The Department Property Administrator is responsible for tagging the equipment. Equipment owned by the federal government cannot be used, and must be tagged "Do Not Use on Non-registered hESC“. Equipment owned by Stanford can be used, and must be tagged "Approved for Use on Non-registered hESC“. Equipment purchased with federal funds and owned by Stanford may be used if it meets one of two criteria. Please read the criteria on the slide.

17. ©National Council of University Research Administrators FRAIX 2008 Equipment Inventory Will Be Conducted Periodically Laboratories where non-registered hESC research is performed are subject to periodic inventories by PMO to ensure that only approved equipment is used to support non-registered hESC research. Additional detail on procedures for equipment when conducting hESC research can be found in the Property Administration Manual, Chapter 14 “Using Equipment for Stem Cell Research”. Laboratories where non-registered hESC research is performed are subject to periodic inventories by PMO to ensure that only approved equipment is used to support non-registered hESC research. Note the resource listed on the slide.Laboratories where non-registered hESC research is performed are subject to periodic inventories by PMO to ensure that only approved equipment is used to support non-registered hESC research. Note the resource listed on the slide.

18. ©National Council of University Research Administrators FRAIX 2008 Allocation Methodology for Materials and Supplies If you purchase expendable materials and supplies that benefit multiple projects, use a reasonable allocation methodology to accurately assign costs to the benefiting projects. This allocation methodology must be documented. When making such purchases to support non-registered hESC research, make certain costs are not allocated to federal projects. To avoid risk of charging materials and supplies for non-registered hESC to federal projects, purchase supplies for non-registered hESC research separate from all other research where practical. For more information on allocation methodologies and documentation, go to the “Allocation” page in the Cardinal Curriculum. If you purchase expendable materials and supplies that benefit multiple projects, use a reasonable allocation methodology to accurately assign costs to the benefiting projects. Be sure to document your methodology! Because you may not allocate any expenses for non-registered hESC research to the federal government, purchase materials and supplies for non-registered hESC research separate from all other research where practical. There is no room for error. For more information on allocation and documentation methodology, go to the Cardinal Curriculum page shown on the slide. If you purchase expendable materials and supplies that benefit multiple projects, use a reasonable allocation methodology to accurately assign costs to the benefiting projects. Be sure to document your methodology! Because you may not allocate any expenses for non-registered hESC research to the federal government, purchase materials and supplies for non-registered hESC research separate from all other research where practical. There is no room for error. For more information on allocation and documentation methodology, go to the Cardinal Curriculum page shown on the slide.

19. ©National Council of University Research Administrators FRAIX 2008 Procedure: Service Centers Service Centers Service Centers required for research with NR hESC must be listed on the hESCRT form at the proposal stage. The Office of Research Administration will verify that the specific Service Center is on the list Service Centers Approved for Non-registered hESC. If, after an award has been made, it becomes necessary for a project engaged in NR hESC research to use a Service Center that was not listed on the hESCRT form, contact the ORA Compliance & Policy Office to request approval.

20. ©National Council of University Research Administrators FRAIX 2008 Derivatives from hESC Research Research using derivatives from non-registered hESC lines may not be supported by federal funds. For costing purposes they are treated just like the lines themselves. Use the SCRT FORM to record: the source of the hESC lines and the hESC derivatives, indicate whether the source is a registered line or non-registered line, and the funding source of your research (termed subsequent research in the Procedures). Derivatives from non-registered hESC lines may not be supported by federal funds. They are treated just like the lines themselves. Use the SCRT FORM to record: the source of the hESC lines and the hESC derivatives indicate whether the source is a registered line or non-registered line list the funding source of your research (termed subsequent research in the Procedures)Derivatives from non-registered hESC lines may not be supported by federal funds. They are treated just like the lines themselves. Use the SCRT FORM to record: the source of the hESC lines and the hESC derivatives indicate whether the source is a registered line or non-registered line list the funding source of your research (termed subsequent research in the Procedures)

21. ©National Council of University Research Administrators FRAIX 2008 Material Transfer Agreements All hESC lines require a Material Transfer Agreement (MTA) or similar agreement in place between the provider and Stanford before the lines can be transferred to investigators. Please review the procedures on the slideAll hESC lines require a Material Transfer Agreement (MTA) or similar agreement in place between the provider and Stanford before the lines can be transferred to investigators. Please review the procedures on the slide

22. ©National Council of University Research Administrators FRAIX 2008 Data & Intellectual Property Researchers may use Data obtained from either registered or non-registered hESC research in subsequent hESC projects if: the data has been published, or permission to use the data has been granted by the original researcher whether the subsequent projects are federally or non-federally funded However, the federal government may not be charged for generating data from non-registered hESC research, or for analyzing or manipulating data for subsequent use in non-registered hESC research. Note that use of Data may be subject to constraints from multiple sources listed on the slide.Researchers may use Data obtained from either registered or non-registered hESC research in subsequent hESC projects if: the data has been published, or permission to use the data has been granted by the original researcher whether the subsequent projects are federally or non-federally funded However, the federal government may not be charged for generating data from non-registered hESC research, or for analyzing or manipulating data for subsequent use in non-registered hESC research. Note that use of Data may be subject to constraints from multiple sources listed on the slide.

23. ©National Council of University Research Administrators FRAIX 2008 Starting the Project Administrative Requirements for Opening a Project Task Award 1. This tutorial and post test have been completed by the PI. The SCRT Form has been completed and submitted. To open a PTA for a hESC research project, the PI must complete this tutorial and post test, and the SCRT form must be completed and submitted.To open a PTA for a hESC research project, the PI must complete this tutorial and post test, and the SCRT form must be completed and submitted.

24. ©National Council of University Research Administrators FRAIX 2008 Further Guidance and Questions Procedures are subject to revision in light of changed circumstances or further guidance from federal officials, the State of California, and the California Institute for Regenerative Medicine, and will be updated on a continuing basis. Any questions you have about the Procedures and their application to specific research projects should be referred directly to the Dean of Research or to the Associate Vice President for Research Administration. Procedures are subject to revision in light of changed circumstances or further guidance from federal officials, the State of California, and the California Institute for Regenerative Medicine, and will be updated on a continuing basis. Any questions you have about the Procedures and their application to specific research projects should be referred directly to the Dean of Research or to the Associate Vice President for Research Administration.