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Questions and Answers on Submitting a New Cell Line

Restrictive Language in Informed Consents

Why Has NIH Proposed to Change the Wording of the Guidelines?

NIH Guidelines and FDA Donor Eligibility Rule


Q: What materials should I consider including in my submission?

A: Relevant materials may include, for example, the consent for donation of embryos for research purposes, the consent for reproductive treatment (including the consent for cryopreservation of embryos, if applicable), and the research protocol or other document(s) demonstrating the relative timing of reproductive treatment and the donation of embryos for research purposes. The materials should be those that were in effect at the time of the embryo donation.

Q: I am an investigator using one of the human embryonic stem cell lines that I received from the NIH stem cell bank. Should I submit a "Request for Human Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research"?

A: Unless your organization has the authority and/or rights pertaining to the human embryonic stem cell line (e.g., your organization is the owner, deriver or licensee or have written permission of the same to submit), you should not submit the request. You can see if a request has been submitted for the line you are using by checking http://grants.nih.gov/stem_cells/registry/pending.htm. (Draft requests can also be seen at http://grants.nih.gov/stem_cells/registry/draft_intent.htm.)

Q: What organization should submit the "Request for Human Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research"?

A: The submitting entity should have the authority and/or rights pertaining to the human embryonic stem cell line (e.g., be the owner, deriver or licensee or have written permission of the same to submit). If you are not sure whether your organization should submit a request, seek appropriate advice from within your organization, such as from your organization's legal counsel.

Q: Who is the Signing Official in my organization?

A: The Signing Official should be an individual with direct or delegated authority to sign on behalf of the organization /submitting entity and verify that the information submitted on Form 2890 is correct. In some cases, this may be an individual who serves as a Signing Official for purposes of submitting grant applications to NIH. Please note that there are Assurance, Certification, and Authority boxes in NIH Form 2890 that should be checked by the Signing Official if he/she is submitting the form. If you are not a Signing Official, do not check the boxes, but provide, as one of the attached supporting documents, a letter signed by the Signing Official that provides the required certifications (see the sample letter in Form 2890).

Restrictive Language in Informed Consents

 

Q: Do the NIH Guidelines for Human Stem Cell Research differ from the human subject regulations at 45 CFR 46 (the Common Rule)?

A: Yes. The July 7, 2009, NIH Guidelines for Human Stem Cell Research require written informed consent in all cases from the individuals donating the embryos. Per OHRP "Guidance on Research Involving Coded Private Information or Biological Specimens" http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.htm, consent is not generally required if the cells cannot be linked to specific living individuals by the investigators, either directly or indirectly through coding systems. In addition, NIH made a policy decision to honor any restrictive language in the informed consent signed by individuals donating human embryos for research, such as statements limiting research using the cells to studies on a particular disease or aspect of development.

Why Has NIH Proposed to Change the Wording of the Guidelines?

 

Q: What exactly do the current Guidelines say and what are you proposing to change?

A:The Final Guidelines, issued on 7/7/2009, state the following:

"For the purpose of these guidelines, “human embryonic stem cells” are cells that are derived from the inner cell mass of the 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."

The proposed revision states:

"For the purpose of these Guidelines, ‘human embryonic stem cells (hESCs)’ are pluripotent cells that are derived from early stage human embryos, up to and including the blastocyst stage, 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."

Q: Why is NIH revising the Guidelines now?

A: NIH recently learned from the scientific community that there are scientifically important sources of human embryonic stem cells (hESCs) that may otherwise meet the strict ethical requirements of the Guidelines, but do not meet the precise definition of hESCs in the current Guidelines. NIH is proposing to make a technical change to the wording of the Guidelines so that they can consider the eligibility of hESCs that have been derived earlier in the development of the embryo. This change would not allow for lines that are derived from embryos that have developed beyond the blastocyst stage. It is important to note that the proposed change to the definition would not alter the rigorous ethical standards in the Guidelines for donation of embryos for hESC research.

Q: Is NIH proposing to revise other aspects of the Guidelines?

A: No. NIH is only proposing this technical change to the definition of hESCs. At some point in the future, the NIH may consider other changes to the Guidelines, per the Executive Order from President Obama.

Q: Why were three hESC lines from Children's Hospital Boston on the Registry put "on hold"?

A: When NIH was asked by a deriver to consider the eligibility of hESCs that do not meet the current definition, the Agency realized that it had inadvertently listed several lines on the Registry that were derived from early stage embryos that had not reached the blastocyst stage. These three lines are temporarily on “hold” and should not be used in NIH-funded research until NIH reviews the public comments on the proposed change to the Guidelines and makes a final decision about a change in the definition of hESCs. At that time, depending on the outcome of the proposed change to the Guidelines, NIH will either take the lines off “hold” status so that they can be used in NIH funded research or remove them from the Registry. It is important to note that these lines met all of the ethical requirements under the Guidelines.

NIH Guidelines and FDA Donor Eligibility Rule

 

A: No. NIH does not require that lines listed on the Registry meet the FDA requirements of 21 CFR 1271 Part C. To be listed on the NIH Human Embryonic Stem Cell Registry, lines must meet the NIH Guidelines for Human Stem Cell Research, which focus on ethical requirements pertaining to the embryo donation process. Thus, the embryo donor screening and testing requirements for relevant communicable diseases agents or diseases in 21 CFR 1271 Part C are not incorporated in the NIH Guidelines. Researchers interested in developing a clinical product, which would be regulated by the FDA, should contact the FDA for more information, ideally prior to donation of the embryo.

See:

Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products and

References for the Regulatory Process for the Office of Cellular, Tissue and Gene Therapies