Information and Instructions for Investigators

Topics Covered

1. Scope of ESCRO review
2. Approval by a University of Connecticut IBC or IACUC and IBC/IACUC Coordination with the ESCRO
3. Approval by a University of Connecticut IRB and IRB Coordination with the ESCRO
4. Sequence of Protocol Submissions to Institutional Research Oversight Committees.
5. Protocol Applications for State of Connecticut Group and Hybrid Proposals
6. Collaborations with Researchers at Other Institutions
7. Transfer of nonhuman animal cells or tissues to University of Connecticut researchers.
8. Transfer of already donated human somatic cells, gametes, or nonembryonic stem cells to University of Connecticut Researchers.
9. Transfer of hESC lines to University of Connecticut Investigators
10. Pre-approved hESC lines
11. The ESCRO Review Process
12. ESCRO Approvals and Renewals
13. Origins and Rationale of the ESCRO Mandate

1. Scope of ESCRO Review

   The ESCRO must review
   • All research funded by the State of Connecticut Stem Cell Research Fund, including those that do not use human embryonic stem cells
   • All stem cell research involving human embryonic stem cells, pluripotent cells and their derivatives
   • All stem cell research involving human gametes and human embryos
   • iPS cell research involving implantation of human cells into pre-natal animals or the central nervous systems of post-natal animals, and iPS research involving the generation of human embryos or other totipotent cells.

   This applies to research at all schools, colleges, campuses, and research arms of the University of Connecticut regardless of the source of funding.

   Stem cell research using human embryonic stem cells, human gametes, or human embryos may not begin and external funds will not be released until ESCRO approval is granted.

2. Approval by a University of Connecticut IBC or IACUC and Coordination with the ESCRO

   • The ESCRO does not replace or duplicate the oversight of institutional Biosafety Committees IBC) and Animal Care and Use Committees (IACUC), or alter the scope of review of these committees. Protocols that normally require IBC and IACUC approval continue to require these approvals. Investigators have the responsibility of submitting the required documents to the relevant oversight committees.
   • ESCRO has the final sign-off on stem cell protocol approvals. Final ESCRO approval will not be given until the ESCRO receives documentation of all required IBC and IACUC approvals.
   • Parallel review with ESCRO and the IBC or IACUC is permitted. Investigators may submit their protocol applications to the ESCRO while IBC or IACUC approval is pending or after it is granted.
   • IBC: All protocols using recombinant DNA or hazardous biological materials must be approved by the University of Connecticut Biosafety Committee(s) at the campus(es) where the research will be conducted.
   • IACUC: All protocols using animals must be approved by the University of Connecticut IACUC(s) at the campus(es) where the research will be conducted.

3. Approval by a University of Connecticut IRB and IRB Coordination with the ESCRO

   • The ESCRO does not replace or duplicate the oversight of the IRB or alter the scope of IRB review. Protocols that would normally require IRB approval continue require IRB approval. Investigators have the responsibility of submitting the required documents to the relevant committees.
   • ESCRO has the final sign-off on stem-cell protocol approvals and will not give final approval until it receives documentation of all required IRB approvals.
   • Because oversight issues of the IRB and the ESCRO are intertwined, it is recommended that the IRB and ESCRO reviews occur in parallel. Investigators should submit a copy of their IRB application to the ESCRO along with their ESCRO application.
   • A University of Connecticut IRB must review and approve stem cell research protocols for:
   1. Informed consent for the donation of human embryos, gametes, or somatic cells from human subjects to University of Connecticut researchers
   2. Receiving and coding for human biological materials with personal donor identifiers
   3. Implanting stem cells into human subjects

   Approval must be obtained from the IRB(s) at the campus(es) where the research will occur.

4. Sequence of Protocol Submissions to Institutional Research Oversight Committees.

   Final ESCRO approval will not be given until the ESCRO receives documentation of all other required protocol approvals from the IBC, IACUC, and IRB, as well as a copy of the MTA for any hESC lines or derivatives.

   To facilitate and expedite the review process, the review of protocols by the ESCRO and other oversight committees may occur in parallel.

   The following sequence of submissions is normally recommended:

   

5. Protocol Applications for State Group and Hybrid Proposals

   State Group and Hybrid grant proposals are composed of several related but relatively autonomous separate projects. A separate ESCRO protocol application should be submitted to the ESCRO for each component project, along with the required supporting documentation for that project (e.g. IBC, IACUC, IRB approvals and a copy of MTAs.)

   A separate application for each component project should also be submitted as required to the IBC, IACUC, and IRB.

6. Collaborations with Researchers at Other Institutions

   If any component of the research project is conducted at an institution other than the University of Connecticut, ESCRO must receive documentation that the relevant approvals (IBC, IACUC, or IRB) have been obtained at the institution where the research is conducted.

   Investigators should identify all collaborating sites on the ESCRO Application Form. The application should clearly indicate which aspects of the research will occur at each site. Final ESCRO approval of the project will not be given until documentation of all required approvals is received.

7. Transfer of nonhuman animal cells or tissues to University of Connecticut researchers.

   Investigators who plan to use nonhuman animal tissues or cells supplied from another researcher or institution should provide the ESCRO with documentation that these materials were obtained with IACUC oversight at the relevant institution.

8. Transfer of already donated human somatic cells, gametes, or nonembryonic stem cells to University of Connecticut Researchers.

   Investigators who plan to use already donated human somatic cells, gametes, or nonembryonic human stem cells must provide the ESCRO with documentation that these materials were obtained with IRB oversight at the relevant institution where the donation occurred, and provide documentation of the informed consent process. The informed consent process must be consistent with the National Academy of Science Guidelines, the regulations of the State of Connecticut, and the standards of the University of Connecticut ESCRO and IRB.

   The State of Connecticut prohibits payment beyond direct expenses to gamete donors for stem cell research.

9. Transfer of hESC lines to University of Connecticut Investigators

   Investigators who plan to use already derived hESC lines that have not been pre-approved by the University of Connecticut ESCRO must provide documentation of their provenance and their ethical derivation. This documentation includes:

   • Evidence of IRB approval at the relevant institution
   • Documentation of the informed consent process in sufficient detail to allow for evaluation of conformity with State of Connecticut Regulations, National Academy of Science Guidelines, and standards of the University of Connecticut ESCRO and IRB.
   • A copy of the MTA (or as soon as it is available)

10. Pre-approved hESC lines

    The ESCRO has approved the following pre-existing anonymous hESC lines for use by University of Connecticut researchers. Investigators should attach a copy of the relevant MTA(s) with their protocol application or forward a copy of the MTA to the ESCRO as soon as it is available.

    • WiCell lines: H1, H7, H9, H13, and H14.
    • ESI lines: hESC3, hESC4, and hESC5.
      (ESI lines hES1 and hES2 are not approved for use by University of Connecticut researchers.)
    • HUES lines # 1-17 from the Melton Laboratory at Harvard University
    • All cell lines banked at the core are approved for use by University of Connecticut Researchers

11. The ESCRO Review Process

1. ESCRO will review all research activities included in a project, including projects spanning several years. A protocol application will not be approved if any one of its component activities is prohibited at the time of review.
2. Each component project of a State of Connecticut Group or Hybrid grant will be reviewed and approved separately. Therefore each project leader should submit a separate ESCRO protocol application.
3. The ESCRO Chair or his/her designee will review the research application and assign the proposal to one of the five categories described below. The ESCRO Chair will notify the researcher of the final result of the review process.
• Category 1. Research that is permissible after administrative review by the ESCRO Chair or his/her designee
• Research funded by the State of Connecticut Stem Cell Fund not involving any human cells or tissues
• Research funded by the State of Connecticut Stem Cell Fund involving in vitro use of human adult stem cells derived from human fetal tissue, placental tissue, or cord blood.
• Category 2. Research that is permissible after approval through an expedited review which is conducted by two members of the ESCRO committee designated by the ESCRO Chair and who report their decision to the ESCRO committee. The category includes but is not limited to the following activities:
• Research using pre-existing anonymous or coded hESC lines or their derivatives in vitro that does not involve the creation of embryos from gametes derived from hES cells.
• Category 3. Research that is permissible after approval through a full committee review. This category includes but is not limited to the following activities:
• Research funded by the State of Connecticut Stem Cell Fund introducing human adult stem cells or human stem cells derived from human fetal tissue, placental tissue, or chord blood into nonhuman animals at any stage of the animals development.
• Research introducing hES cells or their derivatives into nonhuman animals at any stage of the animal's development.
• Research in which the identity of the human donor of embryos, gametes, or somatic cells for hESC research might become known to the investigator.
• Research to derive human embryonic stem cell lines from embryos originally created for reproductive purposes and which are no longer required for such purposes. Appropriate IRB approval must be obtained for the informed consent of the embryos and the value of the proposed research fully supported.
• Parthenogenesis or Androgenesis to Generate Human Embryo-Like Entities
• Category 4. Research Requiring More Stringent Scientific and Ethical Full Committee Review. (May require external review.)

  The ethically sensitive nature of research activities in this category requires a particularly compelling case to demonstrate that there is no less invasive or ethically problematic alternative and that this research has distinctive promise. The scientific validity and ethical appropriateness of a research strategy may alter as the field advances, either increasing or decreasing. Therefore research activities in this category may require evaluation periodically to determine their scientific promise and ethical appropriateness relative to the current state of stem cell science. In no case shall any embryo or embryo-like entity be permitted to develop for more than 14 days or past the point of primitive streak development, whichever occurs first.

  This category includes but is not limited to the following activities:

1. Creation of human embryos for research purposes, including those created from gametes derived from hESC lines
• Requires IRB approval for any gamete donation
2. Human somatic cell nuclear transfer (SCNT) into Enucleated Non-Human Oocytes
3. Human SCNT into Enucleated Human Oocytes
• Requires written procedures and practices to protect human oocyte donors
• Requires refined SCNT techniques that reduce the quantity of required oocytes
• Requires stringent written policies and practices to ensure that derived embryos are used only for the intended research purpose
• Category 5. Research that is prohibited at this time.
• Introduction of hESC cells into nonhuman primate blastocysts or any types of embryonic stem cells into human blastocysts.
• Breeding of an animal into which hESC cells have been introduced at any stage of development
• Implantation into any nonhuman animal or human of any intact human embryo or embryo-like entity created by nuclear transfer.
• In no case shall any human embryo or embryo-like entity be permitted to develop in vitro for longer than 14 days or past the formation of the primitive streak, whichever occurs first.

12. ESCRO Approvals and Renewals

• ESCRO approval will be valid for one year from the date of approval, but the ESCRO reserves the right to review research more frequently.
• Any changes in research activities or additions of hES cell lines must be approved prior to implementation.
• Submission of an ESCRO renewal form is recommended 60 days prior to the date when approval expires.

13. Origins and Rationale of the ESCRO Mandate

    In order to fill a void in federal regulations for human embryonic stem cell research, the National Academies of Sciences (NAS) formulated a set of recommended guidelines for the responsible conduct of human embryonic stem cell research. The formation of institutional embryonic stem cell research oversight committees (ESCROs) is one of these guidelines.

    From a legal perspective the review and approval of human embryonic stem cell (hESC) research by an ESCRO committee or its equivalent is required by the State of Connecticut. From an institutional perspective ESCRO review and approval of hESC research is required by institutional policy. It facilitates the collaboration between researchers across institutions by adopting what are becoming nationally and internationally accepted standards and protects the reputation of the University of Connecticut for its conduct of ethical and responsible research.

    At a deeper level ESCROs exist to protect both the public interest and the progress of biomedical stem cell research. The ethical mandate of the ESCRO is to ensure that appropriate respect is given to the value of human life and to different points of view about the basis of this value. It does so in part by evaluating risks to the value of human life and dignity against possible benefits to human health and well-being. By striving to ensure that only well-justified stem cell research is approved and that inappropriate research is not conducted, ESCROs promote public confidence and trust that stem cell research will be directed towards the improving human well-being and is worthy of public support.