STANFORD UNIVERSITY HUMAN EMBRYONIC STEM CELL RESEARCH
SPECIAL OPERATING PROCEDURES
November 5, 2007

I. Human Embryonic Stem Cell Research Funding Issues

On August 9, 2001, President George W. Bush announced that federal funds may not be used for research using human embryonic stem cell (hESC) lines unless (1) the stem cells were derived from an embryo that was created for reproductive purposes and was no longer needed; (2) informed consent was obtained for the donation of the embryo, 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.

1. Based on the President’s Criteria Stanford Has Identified Two Categories of Human Embryonic Stem Cell Lines:
   
   
   1. Registered Human Embryonic Stem Cell Lines
      Registered hESC lines are those included on the National Institutes of Health (NIH) Human Embryonic Stem Cell Registry http://escr.nih.gov which confirms that the stem cell lines were derived in compliance with the President’s criteria as stated on August 9, 2001. 
      
      Federal funds may be used ONLY for research using registered hESC lines.
      
      
   2. Non-registered Human Embryonic Stem Cell Lines
      Non-registered hESC lines are excluded from the NIH registry because they do not meet the President’s criteria. 
      
      Federal funds may not be used directly or indirectly for research using non-registered hESC lines (or their derivatives).  In addition some nonfederal sponsors have placed restrictions on funding research with non-registered hESC lines; investigators with such funding should review the terms and conditions of the award.
      
      
2. Research on Non-Registered hESC Can Proceed
   
   Although the President’s criteria established on August 9, 2001 bars the use of federal funds for non-registered hESC research, it does not prevent researchers from conducting such research with University or other non-federal funds that do not prohibit such research. To comply with the president’s criteria, however, researchers and institutions that receive both federal and non-federal funding must keep careful account of the expenses associated with non-registered hESC research to ensure that no federal funds are used, directly or indirectly, to support such research. These Procedures reinforce the importance of following Stanford’s established policies and procedures and discuss the precautions needed to ensure that no federal funds are spent directly or indirectly to support non-registered hESC research.  The following procedures in combination with Stanford’s existing policies and procedures will ensure that the federal government does not subsidize non-registered hESC research.

II. Definition of Terms

The terms used in these procedures shall have the following meaning:

Capital Equipment: any tangible personal property having an acquisition cost of $5,000 or greater and a useful life of more than one year.

Data: information and other intellectual property generated from research.

Facilities: laboratory space, offices, and other locations owned or operated by Stanford and used in the conduct of research.

Materials and Supplies: consumable goods with an acquisition cost of less than $5,000 and a useful life of one year or less.

Non-Capital Equipment or Durable Goods: reusable items, including laboratory supplies and equipment, with an acquisition cost of less than $5,000 and an expected useful life of more than one year.

Personnel: all individuals who are or expect to be engaged in work on registered or non-registered hESC research, regardless of funding source, including faculty, post-doctoral fellows, research associates, research assistants, students, and technicians.

Service Centers: provide services that are essential to support the University's teaching and research functions.  Service center activities often result in charges, either directly or indirectly, to federally sponsored grants and contracts. Therefore, service center policies and practices reflect government regulatory costing principles.

Stanford University has promulgated these Special Operating Procedures (Procedures) primarily for non-registered hESC research in accordance with federal hESC research restrictions to clarify steps researchers and administrators must take to ensure that non-registered hESC research can proceed unimpeded and in keeping with the University’s commitment to openness in research. The Procedures describe steps to take in managing resources used for non-registered hESC research.  These Procedures are supplemental to, and in no way take the place of, existing policies and procedures that govern all research.

The Procedures are subject to revision in light of changed circumstances or further guidance from federal law and regulations, California law and regulations, and the California Institute for Regenerative Medicine, and will be updated on a continuing basis.

Responsibilities
Schools where Principal Investigators conduct non-registered hESC research must develop internal processes to ensure compliance with these Procedures.  The Office of Research Administration is responsible for financial and administrative oversight and advising schools, departments and principal investigators in implementing these special operating procedures.  The Dean of Research is responsible for providing oversight for The Stem Cell Research Oversight (SCRO) Committee and interpreting policy, and provides guidance on derivatives and data.

Required Training
Because of the complexity of rules and restrictions associated with hESC research, all University personnel who plan to engage in its conduct, are required to complete a tutorial before they may begin work on any project involving hESC (registered or non-registered). The tutorial titled Human Embryonic Stem Cell (hESC) Research Special Operating Procedures in the Cardinal Curriculum provides an overview of procedures to be observed. It is the PI’s responsibility to ensure all personnel associated with the project complete the required training prior to beginning work on the project. The tutorial can be found at: http://ora.stanford.edu/hesc.

1. Institutional Oversight of Human Stem Cell Research
   
   
   1. Stem Cell Research Oversight Committee
      In order to provide appropriate oversight of hESC, Stanford University has established the Stem Cell Research Oversight (SCRO) Panel.  All University research projects involving human stem cells must be reviewed and approved by the SCRO Panel.  Such review by the SCRO Panel shall be in accordance with all relevant University policies, federal and state regulations. The SCRO Panel, reporting to the Dean of Research, is responsible for providing scientific and ethical review of all proposed research projects involving all human stem cells.  This review is in addition to other reviews that may be already required such as IRB, IACUC, EH&S, etc.  Under no circumstances may the research begin before these approvals are granted.   
      
      
   2. The Human Embryonic Stem Cell Research Tracking Form (hESCRT form)
      The hESCRT form documents and initiates compliance requirements for subsequent review by the appropriate University unit. The hESCRT form must be completed for all research that involves the use of human embryonic stem cells, regardless of the funding source (gifts, departmental research funds, University research funds, or externally-funded research grants or contracts). The form must be completed and routed (1) at the time of proposal for an externally-sponsored project, or (2) prior to the anticipated start date of a project funded by gift, departmental, or University research funds. The form must be reviewed and approved by the school, who will then forward it to ORA.  The form must be updated with changes, (i.e. addition of personnel, change in cell lines, additional funding source, and change in project location) and submitted for review/approval.  Principal Investigators are required to complete and submit a hESCRT form for review/approval on an annual basis. The form can be found at: http://med.stanford.edu/rmg/forms.html#human.

1. Costing Procedures to Ensure that Federal Funds Are Not Used to Support Non-Registered hESC Research
   
   
   1. PTA Setup
      
      Each research project utilizing non-registered hESC, whether it is funded by gifts, departmental research funds, university research funds, or externally-funded research grants or contracts must be accounted for in its own project task award (PTA).  The award purpose must be designated as registered, non-registered or mixed (both registered and non-registered) according to the type of cell lines used.  A PTA can be opened once the Principal Investigator (PI) has completed required training and met the other requirements described within this document.  The PI must also ensure that all laboratory personnel complete required training prior to beginning work in the lab.
      
   2. Allocation of Expense
      
      In labs where both research supported by federal funds is conducted and where non-registered hESC research is conducted, proper allocation of expense, in relationship to use, must be achieved.  In order to prevent federal funds from supporting research on non-registered hESC lines, personnel must develop, document and utilize a reasonable allocation methodology to assign costs to benefiting projects.  Information can be found at:  http://www.stanford.edu/dept/ORA/cardinal/cost_principles/allocability.html.
      
      
      1. Work Effort: Tracking, Allocation, and Certification
         Stanford’s existing policies for tracking, allocating and confirming effort on sponsored projects for all personnel must be used to ensure that effort devoted to non-registered hESC research is not paid with federal funds.  Confirmation of effort on sponsored projects is achieved through monthly review and quarterly certification of expenditure statements by the Principal Investigator.  Information on effort allocation can be found at: http://ora.stanford.edu/cardinal/level_1/reg_environ/direct_cost/effort.asp.
         
         All personnel working on a project with multiple sources of support must pay particular and exacting attention to the proper allocation of salaries and benefits. Salary must be allocated and charged to all benefiting accounts (PTAs) including, gift, departmental, and/or sponsored research accounts (PTAs) commensurate with the effort put forth on each of the projects.
         
      2. Postdoctoral Fellows and Students Funded by Federal Funds/Training Programs
         Postdoctoral fellows and students who are 100% funded by federal training programs, depending on the source of funding, are generally permitted under the terms of their funding to engage in limited or part-time work (not to exceed 8 hours per week) beyond that commitment when the work is unrelated to their training program. In these cases, effort on non-registered hESC research must be compensated and comply with the terms of the award and relevant Stanford policies.  http://www.stanford.edu/dept/DoR/GSH/Sec1C.html#Fin9.
         
         Those who are funded less than full time (50% for a Research Assistantship or less than 100% on a Fellowship) may engage in limited or part-time work beyond those federally funded commitments unless prohibited under the terms of the award.  In these cases, effort on non-registered hESC research must be compensated as part-time employment and must not exceed what is considered full-time effort.
         
         
2. Facilities
   
   Federal Facilities
   Federal facilities, such as the Veterans Administration facility or the Stanford Linear Accelerator Center, may not be used in conducting non-registered hESC research.
   
   Stanford Facilities
   Stanford facilities, on or off campus, may be used in conducting hESC research if the facility has been appropriately authorized by the School, and is identified on the hESCRT form.  In addition, to ensure federal funds were not used in the facilities housing non-registered hESC research  those facilities must be included on the list of approved hESC spaces compiled by the Office of Research Administration.
   
   The following Procedures must be used for Stanford facilities where non-registered hESC research is conducted.
   
   
   1. Track Facility Usage on the hESCRT form
      The PI or designee must list all space where non-registered hESC research is performed on the hESCRT form. This includes ancillary support rooms such as tissue culture rooms, and freezer storage areas.
      
      
   2. Code Space Inventory in iSpace
      The University Space Coordinator must use current space inventory procedures to perform the following.
      
      
      1. Code rooms used for non-registered hESC research, as: organized research (for sponsored research, University research, or cost sharing) or departmental research.
         
         
      2. Document the funding source for non-registered hESC research in the Research Explanation field in iSpace.
         
         
      3. Select a value from the pick list in the Special Use field for the function code of iSpace to show the type of stem cell research the PI is performing in the room. It is essential that the University Space Coordinator update the iSpace system as the type of stem cell research changes.  A list of University Space Coordinators and space inventory procedures can be found at: http://ora.stanford.edu/space/default.asp.
      
      
   3. Changes in Facilities
      If a facility change is contemplated, the PI or designee must update and re-route the hESCRT form indicating the new building and room number.
      
      For Non-Registered hESC Research
      If the facility change is to an existing approved facility, the move can be done prior to updating the form. If the facility to be utilized is not an approved facility then the hESCRT form must be updated and approved prior to the use of the facility.  Once the space is approved, University Space Coordinators must update the iSpace system with any changes. A list of approved facilities can be found at http://ora.stanford.edu/hesc/default.asp
   
   
3. Capital Equipment
   
   The following Procedures must be used for obtaining approval for the use of capital equipment located in spaces where non-registered hESC research will be performed:
   
   
   1. Approving Capital Equipment for Use where Research on Non-registered hESC or their Derivatives Will Be Conducted
      The eligibility of capital equipment for approval is based on ownership, funding, and other applicable restrictions. The Property Management Office (PMO) will assist the Department Property Administrator (DPA) in developing an accurate list of eligible capital equipment using information listed on the hESCRT form. This activity may include a physical inventory, or other means of verification.
      
      
      1. Existing Capital Equipment
         PMO will review the list of existing capital equipment and determine which items may be used on non-registered hESC research. Upon completion of this review, the capital equipment must be marked as described below.  PMO will provide the appropriate hESC tags to the DPA and request confirmation that the tags have been affixed to the capital equipment.  
         
         
      2. Introducing Additional Capital Equipment
         The DPA must inform PMO when capital equipment is purchased, otherwise acquired or introduced into the non-registered hESC research space.  The DPA will review the capital equipment for hESC eligibility in the capital equipment requisition review process. This will include a review of funding sources to determine the capital equipment’s eligibility for use on non-registered hESC.  The DPA will notify PMO of the review results.  PMO will provide the appropriate tags to the DPA and update the capital equipment record during the financial reconciliation process.  PMO should be consulted if there is any doubt whether a piece of capital equipment is approved for use based on these Procedures.
         
         All capital equipment must be recorded in the Sunflower property database and marked with both a Stanford identification barcode and the appropriate hESC use tag (see below).
         
         
      3. Capital Equipment Categories
         
         
         1. Capital equipment NOT ELIGIBLE for use on non-registered hESC research
            
            
            • Capital equipment owned by and whose title remains with the federal government or,
              
              
            • capital equipment which has use restrictions, including those specified by a non-federal sponsor or,
              
              
            • capital equipment purchased with federal funds to which Stanford has title and the funding grant or contract is still active, including the discrete competitive segment that funded the capital equipment.
              
              
         2. Capital equipment ELIGIBLE for use on non-registered hESC research
            
            
            • Capital equipment owned and paid in full by Stanford without support of any federal or otherwise restricted funds or,
              
              
            • capital equipment not subject to any other use restrictions, including those imposed by non-federal sponsors, or
              
              
            • capital equipment owned by Stanford and whose acquisition has been supported wholly or in part by federal funds only upon confirmation of the following by PMO.
              
              
              1. The competitive segment of or the federal grant or contract funding the capital equipment purchase is closed and Stanford retains title to the capital equipment without restriction, or
                 
                 
              2. The federal grant or contract funding the capital equipment purchase is active, and Stanford has reimbursed the award the entire portion of federal funding used to purchase the capital equipment.  This reimbursement must be made using CIRM or non-restricted University funds.
                 
                 
         3. Capital equipment for which a percent is ELIGIBLE for use on non-registered hESC research
            
            The federal grant or contract funding the equipment purchase is active, and the purchase was partially and appropriately allocated to an appropriate non-federal or University-funded source.  The non-federal or University portion can be used on non-registered hESC.  The allocation must be documented and usage on hESC cannot exceed the non-federal or University-funded portion. The non-federal and University-funded portion must be flagged in the University asset tracking system (Sunflower) as unallowable to exclude the cost from the indirect cost pools.  Equipment with joint funding shall be tagged with a maximum percentage of usage allowable on non-registered hESC.
            
      4. Tagging Capital Equipment
         
         Capital equipment reviewed for use on non-registered hESC research must be marked with a Stanford identification barcode and one of the following tags:
         
         
         Capital equipment NOT eligible for use:
         
         
         
         Capital equipment ELIGIBLE for use:
         
         
         
         Capital equipment for which a percent is ELIGIBLE for use:
         
         
         
         
      5. Periodic Inventories
         Space where non-registered hESC research is performed will be subject to periodic physical inventories by PMO to verify that capital equipment used in support of non-registered hESC research is approved and appropriately marked.
         
         
4. Materials, Supplies, Durable Goods, and Non-Capital Equipment
   
   Materials, supplies, durable goods, and non-capital equipment must be evaluated for use in non-registered hESC research.
   
   
   1. Existing Inventory:
      Items, in the existing inventory may not be used to support non-registered hESC research unless they meet one of the following criteria.
      
      
      • The competitive segment or the federal grant or contract under which they were purchased is closed and, there are no further restrictions. However, first preference to use must be given to a subsequent competitive segment.
        
        
      • The federal contribution is reimbursed by Stanford, and there are no further restrictions.  This reimbursement must be made using CIRM or non-restricted University funds.
        
        
      • They were originally purchased with non-federal, or non-restricted funds.
        
        
   2. New Purchases
      Any combination of funds may be used to purchase non-capital items. In order to prevent federal funds from supporting research on non-registered hESC lines, staff must develop, document and utilize a reasonable allocation methodology to assign costs to benefiting projects.  http://www.stanford.edu/dept/ORA/cardinal/cost_principles/allocability.html
      
      
5. Service Centers
   
   Service Centers required for research with non-registered hESC must be listed on the hESCRT form at the proposal stage.  University Officials (ORA Policy and Compliance) 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 non-registered hESC research to use a Service Center that was not listed on the hESCRT form, contact ORA Policy & Compliance to ensure the Service Center has been approved.

V. Other Requirements

1. Material Transfer Agreements
   
   The transfer of hESC lines into or out of the University must be authorized under a Material Transfer Agreement (MTA) signed by: (1) Stanford's Industrial Contract Office (ICO); (2) the receiving researcher (at Stanford); and (3) the providing or receiving party (not at Stanford). An MTA typically obligates the recipient and the recipient’s employer to abide by specific restrictions and limitations on use of the cells, consistent with the consent obtained at the cells’ derivation, and with applicable federal and state laws and regulations.  Before finalizing an MTA for stem cells brought into the University, the Industrial Contracts Office (ICO) requires confirmation that the investigator’s hESCRT has been submitted, and is approved by the SCRO Panel and any other required reviewers. The fully executed MTA must be in place before cells are received in a Stanford lab.  For more information on MTAs go to:  http://www.stanford.edu/group/ICO/agmts/mta.htm
   
   
2. Derivatives from hESC Research
   
   

   To ensure compliance, the PI must determine and record the source of the human embryonic stem cells and human embryonic stem cell derivatives on the hESCRT form. The PI for each project must determine if usage of derivatives is allowed based on the terms of the funding, federal and state laws. Use of derivatives shall be reviewed with the SCRO Manager. The term derivatives does not refer to data obtained from such research, which is addressed in a separate section below.

3. Derivatives from Research other than hESC Cell Research
   
   Derivatives from research other than hESC research include but are not limited to antibodies, plasmids, research tools, reagents and other vectors. Such non-hESC derivatives may be used in the conduct of non-registered hESC research when 1) the derivatives are not needed to carry out the research from which they resulted, 2) the competitive segment from which the derivatives resulted is completed or the data regarding those derivatives has been shared, and 3) the award’s terms and conditions do not prohibit the use of such derivatives.
   
   
4. Data Derived from hESC Research
   
   Researchers may use data obtained from either registered or non-registered hESC research in subsequent hESC projects if 1) the data has been published or 2) permission to use the data has been granted by the original researcher, whether the subsequent projects are federally or non-federally funded. Those investigators with federally funded projects may use, analyze, and present data produced from other studies, including studies that use non-registered hESC cell lines, provided this use is focused on an objective consistent with the scope of work supported with the funds. 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. Data usage is subject to the usual consideration of third-party intellectual property rights, or other rights, as well as any specific grant or contractual constraints on data usage imposed by the providers or sponsors of the data, including other research institutions and state or federal funding agencies.
   
   
5. Further Guidance and Questions
   
   These Procedures are subject to revision in light of changes in federal law, California law, federal and state regulations, and guidance from the California Institute for Regenerative Medicine (CIRM), and will be updated on a continuing basis.  These procedures address only hESC – related issues, and do not supersede or replace any other University policy or procedure.
   
   Any questions 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.