November 14, 2008
SUBJECT: Policy and Guidelines for the Conduct of Research Involving the Use of Human Embryonic Stem Cells
SUPERSEDES: GIM 36, June 1, 2007
On August 9, 2001, President George W. Bush announced that federal funding could be used to support human embryonic stem cell research but only with respect to stem cell lines that had already been derived as of that date. The announcement stated that use of federal funds would be limited to research on existing stem cell lines that were derived:
In addition, the announcement expressly stated that no federal funds could be used for:
President Bush also stated that in order to ensure that federal funds were used to support only stem cell research that is scientifically sound, legal, and ethical, he was directing the National Institutes of Health to examine the derivation of all existing stem cell lines in order to create a registry of those lines that satisfy these criteria.
Subsequent to August 9, 2001, the National Institutes of Health established a human embryonic stem cell registry listing those stem cell lines that are eligible for federal funding support. Human embryonic cell lines not currently listed in the registry are considered “ineligible” and may not be used in federally funded research. Except for the prohibition against use of federal funds for research using ineligible stem cells, the federal government does not otherwise restrict research involving the use of ineligible cell lines. As a result, research utilizing cell lines not listed on the registry may be conducted at institutions receiving federal support providing the research is supported solely by non-federal funds. To comply with federal requirements, institutions that receive federal research support must have adequate controls to assure that no federal funds are expended, either directly or indirectly, in support of the ineligible research. In order to accomplish this, researchers and institutions must carefully monitor costs, expenditures and use of resources in a manner that assures that expenditures for this ineligible research are treated as “unallowable” under applicable federal accounting rules.
As research with human embryonic lines has increased, there has been a recognition within the research community that additional guidelines were needed, partly to address the lack of applicable federal regulations for research with ineligible cell lines and partly to address a growing awareness of important scientific and ethical questions in this field. As a result of these concerns, the National Research Council and the Institute of Medicine of the National Academies established the “Committee on Guidelines for Human Embryonic Stem Cell Research” whose purpose was to review this field of research and to develop appropriate recommended guidelines. In April 2005, the National Academies published a major report, (amended in 2007) entitled “Guidelines for Human Embryonic Stem Cell Research” which provides an ethical and legal framework for the responsible conduct of all human embryonic stem cell research. The fundamental recommendation of the amended report is the establishment of oversight through a local committee that is charged with reviewing and approving research protocols. The committee does not replace an institution’s local institutional review board having authority over human subjects research, but instead is charged with assurance that the research has scientific and ethical merit and that the provenance of the cells used in the research has been adequately established. The committee’s report also offers guidance for institutional review boards as they consider stem cell research proposals requiring human subjects research review and approval.
The federal requirements and limitations with respect to human embryonic stem cell research and the amended 2005 National Academies guidelines are the foundation of the University’s policy in this area and for GIM 36. GIM 36 sets forth a number of requirements for the conduct of human embryonic stem cell research, including segregation of federal and non-federal funding for research using “ineligible” cell lines and oversight of research through a standing committee.
The University of Washington believes that research utilizing human embryonic stem cells is essential to expanding fundamental scientific knowledge of cellular and developmental human biology. The University has further concluded that such research offers a significant potential to develop treatments for a large number of serious and debilitating human diseases, disorders and health conditions, including genetic diseases, tissue injuries, and degenerative diseases such as heart disease, spinal cord injuries, and various diseases of the nervous system. It is the University’s policy to permit and encourage qualified investigators to engage in responsible and ethical research requiring the use and derivation of human embryonic stem cells, human embryonic germ cells, and human adult stem cells obtained from any source, providing the cells are obtained and the research is conducted with appropriate oversight and in accordance with all applicable laws, rules and regulations.
The UW has expressly prohibited certain activities relating to human embryonic stem cells, such as human reproductive cloning, which are described in greater detail in section V.C., below.
For purposes of GIM 36, the following definitions shall apply:
All UW personnel engaged in hESC research and all persons engaged in hESC research utilizing any UW facilities, equipment or other resources shall do so only in compliance with all applicable federal, state, and local laws, regulations, and policies.
All UW personnel engaged in hESC research and all persons engaged in hESC research utilizing any UW facilities, equipment or other resources shall do so only in compliance with all applicable UW policies, regulations, and procedures, including without limitation GIM 36 and other policies, regulations, and procedures relating to the following:
No UW personnel shall engage in and no UW facilities, equipment or other resources shall be utilized for any of the following:
The following Research and/or other activities are not subject to GIM 36 and are exempt from review by the ESCRO Committee.
All hESC research conducted at the UW that is classified as “Sponsored Research” under Grants Information Memorandum 34 shall be processed through OSP on a Form eGC1. All hESC research conducted at the UW that is not classified as “Sponsored Research” under Grants Information Memorandum 34 shall be processed in accordance with established rules and procedures. hESC research shall only be conducted after all generally required UW approvals have been obtained for such research.
At the discretion of the Vice Provost for Research, one or more of the foregoing five researcher positions may be filled through the appointment of two persons to serve as alternate voting members designated to hold a single position. Alternate voting members shall have similar expertise and share all responsibilities for the position and alternate attendance at meetings of the ESCRO Committee. Alternates shall also be entitled to attend ESCRO Committee meetings in a non-voting capacity, but on such occasions may not participate in decisions or deliberations of the ESCRO Committee.
To ensure consistent and efficient processing of hESC research proposals requiring IRB review, the UW Human Subjects Division shall designate a single IRB committee as having exclusive jurisdiction to review all hESC research proposals requiring IRB approval. In carrying out their reviews, the IRB and ESCRO Committee shall strive to coordinate their activities to avoid unnecessary overlap and duplication of reviews and shall cooperate in the sharing and interchange of information to the extent permitted by applicable rules and regulations.
Investigators shall procure hESC and hESC lines consistent with GIM 36 and UW purchasing rules and regulations. Upon procurement, the Principal Investigator having authority over such newly-acquired hESC and/or hESC lines shall promptly transmit required information to the ESCRO Committee for entry into the UW hESC registry described in section V.K. below. hESC and hESC lines shall only be transferred to other investigators, both at the UW and outside the UW, and to other organizations consistent with the provisions of GIM 36 and other applicable UW rules and regulations.
Through the establishment of a centralized registry prescribed by the ESCRO Committee, the UW will maintain a record of all hESC lines, including new hESC derived cell lines, kept at UW facilities. The UW hESC registry will be supported and maintained within the UW Office of Research and will contain information about the source and provenance of hESC lines, the location of the hESC lines, the name of the investigator responsible for the safekeeping of the hESC, disposition of hESC lines, and such other information the ESCRO Committee deems appropriate.
Through the establishment of a centralized database prescribed by the ESCRO Committee, the UW will maintain a record of all hESC research both occurring in UW facilities or involving UW personnel. In cooperation with OSP and the UW’s System to Administer Grants Electronically (SAGE), the UW hESC research database will be supported and maintained within the UW Office of Research and will contain information identifying the investigators conducting hESC research, including the PI, the funding source of the research, OSP and other relevant UW identifying numbers, the period of the research, a brief description of the research, and such other information the Vice Provost for Research deems appropriate.
Any tissue banks or repositories at the UW containing hESC and hESC lines, including new hESC derived cell lines, shall be subject to subject to the requirements of GIM 36 and shall be included within the UW hESC registry described above.
As a condition of and prior to conducting hESC research, investigators are required to be familiar with applicable UW and other compliance policies, rules and regulations governing such activity, including GIM 36. The ESCRO Committee will recommend to the Vice Provost of Research a hESC compliance training program that will be sufficient to demonstrate knowledge of these policies. The content of such training shall include information on categories of hESC research, requirements for ESCRO Committee reviews, documentation of compliance, permitted and prohibited use of federal funds, human subjects research issues, and such other matters the ESCRO Committee deems appropriate. The training program shall provide instruction by means of a one-hour seminar, either delivered in person, online or through written materials.
The UW Institute for Stem Cell and Regenerative Medicine (ISCRM) has been established for the purpose of facilitating and encouraging basic research on hESC in order to develop therapies and cures for human disease. In making decisions about policies and procedures governing the conduct of hESC research, the UW and the ESCRO Committee will provide reasonable opportunities for investigators who are part of ISCRM to express their views on such matters and take into account such views in making decisions. The ESCRO Committee and ISCRM will strive to cooperate in establishing efficient mechanisms for review of hESC research proposals and the training of hESC research investigators.
In order to carry out ineligible hESC research at the UW, the UW is required to maintain careful records documenting that no federal funds are used, either directly or indirectly, to support research involving the use of hESC not listed on the NIH hESC registry.
The UW is providing these guidelines, which are consistent with federal hESC research restrictions, in order to set forth the steps that researchers and administrators can take to ensure that hESC research can proceed unimpeded at the UW. These guidelines describe steps to take in managing resources used for hESC research, including (1) facilities, (2) equipment, (3) personnel, (4) materials, supplies, and other commodities, (5) non-capitalized equipment, (6) purchased services, (5) derivatives from hESC research, and (6) data and intellectual property associated with hESC research.
These guidelines are intended to address only those issues presented by current federal hESC research policy. They supplement, but do not replace, other UW financial and accounting policies, rules and procedures.
In addition to the definitions set forth in Section IV, Definitions, above, the following definitions shall apply to these cost-allocation guidelines:
The cost principles set out in 2 CFR 200 do not prohibit institutions that receive federal support from engaging in "unallowable" activities. Instead, they restrict the use of federal funds to pay for these activities. For example, Subpart E-COST PRINCIPLES of 2 CFR 200 states that the costs of bad debts, donations and contributions, and entertainment (among others) are generally unallowable. Thus, while researchers may make a personal choice to celebrate a colleague's accomplishment at a local restaurant, it is not appropriate to charge the cost of that celebration to the federal government. Even though certain costs are unallowable, the UW and its researchers may still be reimbursed for other allowable expenses incurred in connection with federally supported projects.
Subpart E-COST PRINCIPLES of 2 CFR 200 indicates that a federally-supported institution can avoid the impermissible shifting of costs of unallowable activities to the federal government if it does not either (1) impose the direct costs of such activities on the federal government, or (2) request reimbursement from the federal government for F&A costs associated with unallowable activities. Examples of indirect costs are building depreciation, maintenance expenses, library expenses, and student and departmental administration expenses.
To determine whether a particular direct cost can be charged to the federal government, the cost must be allowable, reasonable, and allocable to work conducted under federally sponsored agreements, and it must not include any unallowable costs.
Although the direct costs of unallowable activities may not be charged to the federal government, the government will pay its share of resources that are used for both federal and non-federal purposes. Subpart E-COST PRINCIPLES of 2 CFR 200 states that "a cost is allocable to a particular cost objective (i.e., a specific function, sponsored agreement, department, or the like) if the goods and services involved are chargeable or assignable to such cost objective in accordance with relative benefits received or other equitable relationship." For example, if personnel time or general-purpose laboratory materials are being used for both federally sponsored research and ineligible hESC research, the federal government will pay the cost of that proportion of the resource being used for federally sponsored research.
In general, UW F&A costs are calculated and allocated to the federal government by multiplying the direct costs of a federal project by the government-approved UW F&A rate. This approach assumes that there is an established relationship between the direct costs of research projects and the F&A costs as reflected in the F&A rate and that it is therefore possible to identify the F&A costs associated with a particular project by applying the predetermined rate to the total amount of direct costs associated with the project. The NIH guidance on hESC research indicates that the indirect costs of ineligible hESC research are subject to this approach. As a result, the costs of ineligible hESC research may be included in the regular F&A cost allocation base, and associated indirect costs may be allocated pursuant to ordinary cost allocation principles. The NIH Frequently Ask Questions on this subject states that compliance with these methodologies “will prevent the shifting of unallowable stem cell research costs to federally sponsored programs.”
In addition to obtaining required approvals to conduct hESC research, a PI engaged in ineligible hESC research must obtain confirmation from the PI’s school or college that the proposal conforms to the guidelines set out below.
These cost-allocation guidelines apply to facilities, equipment, personnel, materials, supplies, non-capitalized equipment, and purchased services, devoted in whole or part to eligible or ineligible hESC research, regardless of funding source. The schools and colleges are responsible for implementing the guidelines for these specific resources, in consultation with OSP, including recharge and cost centers involved in hESC research activities.
UW facilities may be used to conduct hESC research only if they are approved for that use in advance. NIH guidance specifically provides that an investigator receiving NIH support may create new hESC derived cell lines and engage in other ineligible hESC research providing (i) all direct costs of such activities are allocated to a non-federal funding source, and (ii) the UW has in place a reasonable method of separating costs so that the appropriate F&A costs allocable to the ineligible hESC research are allocated to non-federal accounts so as to prevent federal funds from improperly supporting ineligible hESC research. Prior to commencing hESC research, the PI must (i) have written confirmation from the school or college that the facility has been approved for use in the conduct of hESC research, and (ii) adhere to any limitations contained in the written approval regarding the usage of facilities and related recordkeeping. The following guidelines apply to the approval of facilities in which hESC research is conducted:
UW equipment may be used to conduct ineligible hESC research with advance approval of the school of college. According to current NIH guidance, the acquisition of equipment used in the conduct of ineligible hESC research may not be federally supported. Federal regulations (45 CFR §§ 75; 2 CFR 200.313) contain additional rules that restrict the use of federally-owned equipment or other equipment acquired with federal funds. Prior to commencing hESC research, the PI must (i) have written confirmation from the school or college that the equipment has been approved for use in the conduct of hESC research and (ii) agree to any limitations in the written approval regarding the use of equipment and related recordkeeping. Limitations may involve, for example, restrictions on time or percentage limits on equipment capacity. The following guidelines apply to the approval of equipment to be used in hESC research:
As provided in GIM 36, all UW personnel participating in hESC research must have prior approval from the UW regardless of whether the research is eligible for federal funding and whether any of the personnel receive federal funding for any purpose. Prior to commencing hESC research, the PI must (i) ascertain that any required approvals have been obtained from the ESCRO Committee, (ii) obtain written approval on Form eGC-1 from the school or college to conduct the research, and (iii) obtain the agreement of all UW personnel participating in the hESC research to follow all UW rules and procedures regarding hESC research, including GIM 36 and these hESC cost-allocation guidelines. In addition to the foregoing, the following rules apply to the approval of personnel to participate in hESC research, regardless of funding source:
Materials, supplies, non-capitalized equipment, and purchased services owned or acquired by UW may be used in conducting ineligible hESC research. Prior to commencing hESC research, the PI must (i) determine, for cost-allocation purposes, which materials, supplies, non-capitalized equipment, and purchased services were purchased specifically to carry out ineligible hESC research, (ii) agree to recordkeeping requirements for tracking the usage of general-purpose materials, supplies, non-capitalized equipment, and purchased services, to ensure that the federal government is not charged for ineligible hESC research. The school or college, in consultation with OSP, is responsible for ensuring that these requirements are followed. For acquired materials, supplies, non-capitalized equipment, and purchased services this should be done through separate budgets and/or other appropriate financial accounting methods. The following guidelines apply to the usage of materials, supplies, and purchased services:
Researchers may use data, information and intellectual property obtained from any hESC research in subsequent hESC research, regardless of whether the subsequent projects are federally or non-federally funded. However, the federal government may not be charged for generating data from ineligible hESC research, or for analyzing or manipulating data for subsequent use in ineligible hESC research. These cost-allocation guidelines govern the determination as to whether resources engaged in the generation, analysis, or manipulation of data from hESC research may be charged to the federal government. Any use of data is subject to the usual consideration of third-party intellectual property rights, as well as any specific grant or contract constraints on data usage imposed by the suppliers or sponsors of the data, including other research institutions and federal funding agencies.
These cost-allocation guidelines are subject to revision in light of any changes in law, rules or regulations. Any questions about these guidelines and their application to specific research projects should be referred through the school or college. In addition, specific questions about costing issues for grants, cost centers, and recharge centers should be referred to the UW Office of Grant and Contract Accounting, Management Accounting and Analysis. In order that UW personnel do not receive conflicting or incomplete information, formal inquiries on behalf of the UW to federal agencies about the application of federal cost principles to hESC research shall be made by OSP.