Boston University and Boston Medical Center. Guidelines for the Use of Human Embryonic Stem Cells (hesc)

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1 Boston University and Boston Medical Center Guidelines for the Use of Human Embryonic Stem Cells (hesc) 1. Introduction Boston University and Boston Medical Center are committed to research that advances human health and scientific progress. In order to facilitate BU and BMC scientists to conduct research in the important field of regenerative medicine, BU and BMC have developed the following Guidelines for the Use of Human Embryonic Stem Cells. Research involving human embryonic stem cells is governed by federal and state regulations, NIH Guidelines on Human Stem Cell Research, and Boston University and Boston Medical Center policies. On March 9, 2009, President Barack H. Obama issued Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The Executive Order stated that the Secretary of Health and Human Services, through the Director of NIH, may support and conduct responsible, scientifically worthy human stem cell research, including human embryonic stem cell (hesc) research, to the extent permitted by law. On July 7, 2009 the NIH issued its Guidelines for the implementation of Executive Order 13505, as it pertains to extramural NIH-funded stem cell research. These guidelines were developed to ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Though the Obama administration has made possible broader funding for work with existing stem cell lines, the federal government is still prohibited by the Dickey-Wicker Amendment from funding any research that involves the destruction of human embryos, including the derivation of new stem cell lines. Therefore the NIH Guidelines specifically state that prior to the use of NIH funds, funding recipients should provide assurances, when endorsing applications and progress reports submitted to NIH for projects using hescs, that the hescs are listed on the NIH registry. All research that involves the use of human stem cells, human embryos, or their derivatives, must be reviewed and approved by the appropriate oversight Committee (e.g. IRB, IBC and/or IACUC) and the Embryonic Stem Cell Research Oversight Committee (ESCRO) as appropriate, prior to the commencement of the activity. 2. Commonwealth of Massachusetts Requirements In 2005 Massachusetts enacted a law known as an Act Relative to Enhancing Regenerative Medicine in The Commonwealth (the Act) authorizing embryonic stem cell research. The Act applies to all embryonic stem cell research in the Commonwealth, and establishes criteria for the types of research permitted and specifically requires that: All institutions that intend to conduct human embryonic stem cell research must obtain a certificate of registration from the Department of Public Health (DPH), valid for 3 years, prior to initiation of such research. BU hesc Guidelines Page 1

2 An institution holding a certificate of registration must submit an annual report to the DPH providing a summary of the research approved during that calendar year and a statement representing that such research was reviewed in accordance with the provisions of the Act, if applicable. 3. National Institutes of Health (NIH) Guidelines The NIH guidelines cover the general criteria for the conduct of human embryonic stem cell research, as well as specific requirements for the use of Federal funds for such research. The NIH states that its guidelines are based on the following principles: Responsible research with hescs has the potential to improve our understanding of human health and illness and discover new ways to prevent and/or treat illness. Individuals donating embryos for research purposes should do so freely, with voluntary and informed consent General Provisions The provisions of the HHS regulation, Protection of Human Subjects, are applicable when research involving human embryonic stem cells constitutes human subject research. The regulation applies, among other things, to research involving individually identifiable private information about a living individual. The HHS Office for Human Research Protections (OHRP) considers biological material, such as cells derived from human embryos, to be individually identifiable when they can be linked to specific living individuals by anyone either directly or indirectly through coding systems, or through data sets or data elements which, if combined, would allow for deductive disclosure. Thus, in certain circumstances, IRB review may be required. Research involving stem cells that are anonymous are exempt from the requirements for IRB review under 45 CFR 46. Please check with the IRB Office to confirm that the specific lines used are exempt.) Note: When using stored tissue or cells that were not collected specifically for the proposed derivation of pluripotent cell lines through an interaction or intervention with a living individual, and that retain no information that would allow the identity of the individual from whom the tissue or cells were originally obtained to be ascertained, the derivation of the cell line is not considered human subjects research under the HHS regulations. Therefore, IRB approval and informed consent would not be required for the derivation of the cell line. When using stored tissue or cells from a deceased donor, the derivation of the cell line would not be considered human subjects research under the HHS regulations because those regulations apply only to living individuals. However, state or local laws may apply (e.g., if material is obtained from autopsy). To ensure that the greatest number of responsibly derived hescs are eligible for research using NIH funding, these Guidelines are divided into several sections, which apply specifically to embryos donated in the U.S. and foreign countries, both before and after the effective date of these Guidelines. Section II (A) and (B) of the NIH Guidelines describe the conditions and review processes for determining hesc eligibility for NIH funds. BU hesc Guidelines Page 2

3 3.2. Use of NIH Funds Uses of NIH funds, awarded after March 9, 2009, are restricted to the hescs lines that are listed on the NIH registry. All previously funded NIH research is subject to the initial provisions of the award, unless the terms and conditions have been subsequently modified. Prior to the use of NIH funds, funding recipients should provide assurances, when endorsing applications and progress reports submitted to NIH for projects using hescs, that the hescs are listed on the NIH registry. Use of these hesc at BU and BMC are allowed subject to compliance with the general provisions of the NIH Guidelines and criteria 3.3. Restriction on the Use of NIH Funds The NIH Guidelines restrict the use of NIH funds for the following research involving the use of hesc: Research Using hescs and/or Human Induced Pluripotent Stem Cells The NIH Guidelines list hescs and human induced pluripotent stem cells as human cells that are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers. Although the cells may come from eligible sources, the following uses of these cells are nevertheless ineligible for NIH funding: Research in which hescs (even if derived from embryos donated in accordance with these Guidelines) or human induced pluripotent stem cells are introduced into non-human primate blastocysts. Research involving the breeding of animals where the introduction of hescs (even if derived from embryos donated in accordance with the NIH Guidelines) or human induced pluripotent stem cells may contribute to the germ line Other Research Not Eligible for NIH Funding The NIH Guidelines also specify the following activities as ineligible for the use of its funds: NIH funding of the derivation of stem cells from human embryos is prohibited by the annual appropriations ban on funding of human embryo research (Section 509, Omnibus Appropriations Act, 2009, Pub. L , 3/11/09), otherwise known as the Dickey Amendment. Research using hescs derived from other sources, including somatic cell nuclear transfer, parthenogenesis, and/or IVF embryos created for research purposes. 4. Research Involving hesc That Is Not Eligible For NIH Funding Based on the NIH Guidelines, all hesc research that is ineligible for Federal funding (i.e. those listed in Sections 3.3) must be conducted in a manner that does not utilize federal funds. Research that is not eligible for NIH funds or with cells not listed on NIH registry (i.e. those listed in Sections 3.3) is permitted at BU BU hesc Guidelines Page 3

4 and BMC. However, the ability of BU and BMC scientists to conduct research that is considered federally non-fundable requires establishment of prudent practices and guidelines for separation of costs associated with hesc activity that are in compliance with federal costing principles such as 2 CFR Part 220 (OMB Circular A-21, Cost Principles for Educational Institutions). The following BU and BMC Guidelines are developed to assist compliance with the Federal restrictions by researchers who also receive federal funding to keep account of the expenses associated with ineligible hesc activity and to ensure that no federal funds are used to support such research BU-BMC Policy BU and BMC establish the following basic criteria for research involving hesc: All activities involving human embryonic stem cell research shall be in accordance with the applicable state and Federal regulations and funding governing such research, including any restrictions on the use of Federal funds for such research. All individuals conducting human embryonic stem cell research that falls under the criteria of human subject research must submit a protocol to the Institutional Review Board (IRB) for review and approval prior to initiation of the study. This must be done even if there are no plans to put such cells into human subjects. Approval must be obtained from the Institutional Biological Safety Committee (IBC), and the Institutional Animal Care and Use Committee (IACUC) if the hesc will be used in animals. Investigators conducting research deriving or using human embryonic stem cells that are not on the NIH Human Embryonic Stem Cell Registry must financially separate the costs of that research and charge the costs to a non-federal funding source. The Embryonic Stem Cell Research Oversight Committee (ESCRO), or delegated representative(s) from the Office of Research Compliance, must review and approve all hesc research that is ineligible for Federal funding. The purpose of the policy is to establish criteria for identification of hesc activity, and procedures for review of such research for compliance with applicable funding requirements. The goal of this policy is to ensure that: BU and BMC are aware of all human embryonic stem cell research activities conducted by the faculty, staff, postdoctoral scholars, students and visiting scholars, including, to the maximum extent possible, the sources or derivation of any human embryonic stem cells planned for use or being used. Each person at BU and BMC working on such research is fully aware of the compliance requirements associated with the work. The federal government's current prohibitions against inappropriate use of federal funds on ineligible hesc research are fully observed. BU and BMC complies with any Massachusetts reporting requirements for such research. BU hesc Guidelines Page 4

5 Provisions exist to monitor compliance with this policy continuously and make changes in it as are deemed appropriate Definitions Covered Equipment: All tangible personal property used in hesc activity with an expected useful life of more than one year and an acquisition cost of $5,000 or more. Data: Information and other intellectual property generated from research. Derivatives: Broadly defined as dead cells, DNA, RNA, proteins, and any other products secreted by or extracted from human embryonic stem cells. Durable Goods: Reusable items, including laboratory supplies and equipment, with an acquisition cost of less than $5,000 per item and an expected useful life of more than one year. Expendable Materials and Supplies: Non-equipment materials such as laboratory and office supplies, chemicals, test tubes, tissue culture materials, purchased services including equipment repair and preventive maintenance contracts, commercial software, other durable goods, etc. with expected useful life of one year or less. Facilities: Buildings (including laboratory space, laboratory support, offices, office support and other locations) owned or operated by BU or BMC and used in the conduct of research, and instruction. Facilities and Administrative (F&A) Costs: Costs that are incurred for common or joint objectives and cannot be identified readily and specifically with a particular sponsored project, an instructional activity, or any other institutional activity. F&A costs are synonymous with "indirect" costs Federal Funds: Federal funds include direct awards for sponsored activities, federal flow through funds, and funds used to purchase or fabricate equipment or facilities. Embryonic Stem Cell Research Oversight Committee (ESCRO) 1 : The Committee designated to meet the recommendation the National Academies. All Human Embryonic Stem Cell Research at BU and BMC is subject to review and approval by the ESCRO. Human Embryonic Stem Cells- hesc: For the purpose of these Guidelines, "human embryonic stem cells (hescs)" are cells that are derived from the inner cell mass of blastocyst stage human embryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers. Although hescs are derived from embryos, such stem cells are not themselves human embryos. 1 Recommended by the Committee on Guidelines for Human Embryonic Stem Cell Research, Board on Life Sciences, Division on Earth and Life Studies, Board on Health Sciences Policy, Institute of Medicine, National Research Council and Institute of Medicine of the National Academies. BU hesc Guidelines Page 5

6 Human Embryonic Stem Cell Research: For the purpose of compliance with the regulations the term human embryonic stem cell research includes research involving those cell lines defined as hesc above. Ineligible hesc Activity: Any research activity that is not eligible for federal funding. Indirect Costs: See Facilities and Administrative Costs. Institutional Review Board (IRB): The Committee with the responsibility for review and approval of all human subject research at BU and BMC that is subject to the HHS definition of human subject research. NIH Guidelines: NIH has issued a "Frequently Asked Questions" (FAQ) document on conducting stem cell research that addresses many of the key questions regarding the requirements for individuals who are conducting research with both federally fundable and non-federally fundable human embryonic stem cell lines. NIH Human Embryonic Stem Cell Registry: These are hesc lines that are listed by the NIH in their registry as those eligible for federal funding and are also referred to as the Registry hesc lines. Non-Human Stem Cell Research: Research involving the derivation and use of stem cells derived from non-humans. Non-Registry hesc lines: All hesc lines not listed on the NIH Human Embryonic Stem Cell Registry. Personnel: All individuals who are,or expect to be, engaged in work on eligible or nonregistry hesc activity, regardless of funding source, including faculty, post-doctoral fellows, research associates, students, and technicians. Purchased Services: Professional contract services; such as the services of consultants, laborers, or maintenance and repair technicians. Registry hesc lines: See NIH Human Embryonic Stem Cell Registry definition Identification and Tracking of Human Embryonic Stem Cell Research In order to identify all research involving the use of human embryonic stem cells, questions relating to the use of human embryonic stem cells must be answered in all applications, or proposals, submitted to the following: Institutional Review Board (IRB) Institutional Animal Care and Use Committee (IACUC) Institutional Biosafety Committee (IBC) Office of Sponsored Programs (OSP) BU hesc Guidelines Page 6

7 Each research project utilizing non-registry human embryonic stem cells must be accounted for in its own project account and fund. Identification of this research should occur at the proposal stage and OSP should flag this type of research in the system Special Requirements for Research Involving Non-Registry hesc Lines BU and BMC have promulgated the following procedures to address research involving non-registry hesc Lines in accordance with Federal hesc activity restrictions, to clarify steps researchers and administrators must take to ensure that hesc activity that is ineligible for federal funding can proceed unimpeded, and in keeping with the commitment to openness in research. The Procedures describe steps to take in managing resources including: Personnel Facilities Equipment Expendable materials and supplies 4.4. Personnel Personnel working with hesc must follow existing policies for tracking, allocating and confirming effort on sponsored projects for all personnel. Extra attention must be given to ensure that effort devoted to research with ineligible hesc lines is not paid with federal funds. Confirmation of effort on a sponsored project is achieved through the review and certification of Personnel Activity Reports (PARs). Responsibility for Seeking Approval. The PI retains primary responsibility for seeking approval for Personnel to engage in hesc activity. Tracking Effort. BU and BMC s existing policies and procedures for tracking and confirming work effort on federally funded research, including pay-rate policies, will apply so that appropriate effort is devoted to commitments under federal grants, and so that other activities, including ineligible hesc activity, are not supported by federal funds Facilities BU and BMC facilities may be used in conducting ineligible hesc activity if they are approved for such use in advance as long as all direct costs attributable to ineligible research are allocated to a non-federal funding source. Approval of space for use is subject to a clear description of the intended use and the percentage of the space that will be used for ineligible hesc research. The following are required before any facility may be used to conduct ineligible hesc activity: The PI retains primary responsibility for seeking approval for facilities to be used in the conduct of hesc activity. As part of the approval process, the PI must disclose all locations where his or her Non-Registry hesc activity will be conducted. BU hesc Guidelines Page 7

8 The PI must have approval from the ESCRO that the facility and specific rooms have been authorized for use in the conduct of ineligible hesc activity. There may exist limitations on the usage of space where facilities have been constructed, outfitted or renovated in whole or in part with federal funds. Other limitations may involve limits on time, allocation of space or percentage use and will take into account the other commitments of the facilities to federally sponsored projects and other University activities. Facilities Cost Analysis must be notified of any accounts and space involving research using ineligible hesc lines in order to ensure proper cost accounting treatment for the Facilities and Administrative Rate proposal. The PI must adhere to limitations, if there are any, contained in the written approval regarding the usage of Facilities and related recordkeeping. Any anticipated change in space usage where ineligible hesc activity is conducted, whether addition or deletion of existing space, or changes in time or percentage of non-registry hesc activity or other usage, is also subject to these protocols Equipment Federal guidelines generally define equipment to mean any tangible personal property expected to have a useful life of more than one year. For purposes of these procedures only, Covered Equipment is considered to be items that have a purchase price of $5,000 or greater and a useful life of greater than one (1) year. BU and BMC have determined that PIs and staff may use Covered Equipment acquired with federal funds for research on non-registry hesc lines only if the federal government has transferred title to the equipment to BU and BMC, and if the fund(s) used to purchase the Covered Equipment is complete. To use equipment purchased with federal funds the PI must: Have written confirmation from the Property Management Office that the Covered Equipment has been approved for use in the conduct of ineligible hesc activity. Agree to limitations, if any, contained in the written approval regarding the use of Covered Equipment and related recordkeeping. Equipment that is owned by BU or BMC, whose acquisition has not been supported by federal funds, and that is not subject to any other funding restrictions, including restrictions imposed by non-federal sponsors if funded by them, may be used in conducting ineligible hesc activity Expendable Materials and Supplies The federal guidelines require that expendable materials and supplies purchased by federal funds not be used for research involving ineligible hesc lines. The Principal Investigator, or their designee, is responsible for developing a plan to ensure the appropriate requirements are met. 5. Further Guidance and Questions For further information or guidance on regulatory requirements pertaining to hesc activity please contact the Research Integrity & Assurance Office. BU hesc Guidelines Page 8