Human fetal tissue research, regulation for the protection of human subjects, stem cells, PHS Act, Research on transplantation of human fetal tissue

4.1.14 Human Fetal Tissue Research

Human fetal tissue is defined as tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion or stillbirth. This definition does not include established human fetal cell lines. Research involving the transplantation of human fetal tissue must be conducted in accordance with applicable Federal, State and local laws as well as the following NIH guidance.

Sections 498A and 498B of the PHS Act (42 U.S.C. 289g-1 and 289g-2) set forth specific requirements and prohibitions on research involving human fetal tissue. Research involving human fetal tissue is also subject to the HHS Regulations for the Protection of Human Subjects. 45 C.F.R. 46.204 and 46.206 may be specifically relevant.

The scientific and ethical challenges associated with research utilizing human fetal tissue make it imperative that researchers and their organizations be fully aware of and in compliance with the Federal requirements, particularly section 498B. When an application involving human fetal tissue research is submitted to NIH, the AOR's signature certifies that researchers using these tissues are in compliance with section 498B of the PHS Act. The statute specifically prohibits any person from knowingly acquiring, receiving, or transferring any human fetal tissue for valuable consideration. The term "valuable consideration" is a concept similar to profit and does not include reasonable payment for costs associated with the collection, processing, preservation, storage, quality control, or transportation of these tissues. Violation of this statute carries criminal penalties that apply to both those that supply and those that acquire human fetal tissue.

Current federal laws and regulations require informed consent for research involving the transplantation of human fetal tissue and for research with human fetal material associated with information that can identify a living individual. Most states require informed consent for the use of fetal tissue in research. Accordingly, NIH expects informed consent to have been obtained from the donor for any NIH-funded research using human fetal tissue.

When obtaining primary human fetal tissue for research purposes, NIH expects grantees and contractors to maintain appropriate documentation, such as an attestation from the health care provider or a third party supplier, that informed consent was obtained at the time of tissue collection.

4.1.14.1 Research on Transplantation of Human Fetal Tissue

Sections 498A and 498B contain additional requirements for research on the transplantation of human fetal tissue for therapeutic purposes conducted or supported by NIH. Under section 498A, the official who signs the application is certifying that the research on transplantation of human fetal tissue will adhere to the following provisions:

  • The woman who donates the fetal tissue must sign a statement declaring that the donation is being made:
    • for therapeutic transplantation research,
    • without any restriction regarding the identity of individuals who may receive the transplantation, and
    • without the donor knowing the identity of the recipient.
  • The attending physician must sign a statement that he/she has:
    • obtained the tissue in accordance with the donor's signed statement and
    • fully disclosed to the donor his or her intent, if any, to use the tissue in research and any known medical risks to the donor or risks to her privacy associated with the donation that are in addition to risks associated with the woman's medical care.
  • In the case of tissue obtained pursuant to an induced abortion, the physician's statement also must state that he/she:
    • obtained the woman's consent for the abortion before requesting or obtaining consent for the tissue to be used;
    • did not alter the timing, method, or procedures used to terminate the pregnancy solely for the purpose of obtaining the tissue for research; and
    • performed the abortion in accordance with applicable State and local laws.
  • The PD/PI must sign a statement certifying that he/she is aware that the tissue is human fetal tissue obtained in a spontaneous or induced abortion, or pursuant to a stillbirth and that the tissue was donated for research purposes. The PD/PI also must certify that this information has been shared with others who have responsibilities regarding the research and, before eliciting informed consent from the transplantation recipient, will obtain written acknowledgment that the patient is aware of the aforementioned information.
  • The PD/PI must certify in writing that he/she has had no part in any decisions as to the timing, method, or procedures used to terminate the pregnancy.

In submitting an application to NIH, the AOR that signs the application is certifying that, if research on the transplantation of human fetal tissue is conducted under the grant-supported project, the organization will make available for audit by the HHS Secretary or designee, the physician statements, the PD/PI's statements, and informed consents required by subsections 498A(b)(2) and (c) of the PHS Act or will ensure HHS access to those records, if maintained by an entity other than the recipient. This requirement is in addition to the requirements concerning human subjects in research.

In addition, FDA has jurisdiction over fetal cells and tissues intended for use in humans and requests that investigators contact them to determine whether any planned or ongoing clinical research would require submission of an IND application. Additional information and FDA contact information is available at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm105857.htm.

4.1.14.2 Human Fetal Tissue from Elective Abortions

Human Fetal Tissue (HFT) from elective abortion is defined as research involving the study, analysis, or use of primary HFT, cells, and derivatives, and human fetal primary cell cultures obtained from elective abortions and includes the following:

• human fetal primary or secondary cell cultures, whether derived by the investigator or obtained from a vendor.

• animal models incorporating HFT from elective abortions, including obtaining such models from a vendor.

• derivative products from elective abortion tissues or cells such as protein or nucleic acid extracts.

• any human extra-embryonic cells and tissue, such as umbilical cord tissue, cord blood, placenta, amniotic fluid, and chorionic villi, if obtained from the process of elective abortion.

NIH requires additional documentation of the use of HFT from elective abortions in research, as NIH does with other research materials and models, to ensure that it is utilized for research only when scientifically justifiable, and in the least amount possible to achieve the scientific outcomes. NIH requires applicants to provide detailed information addressing the use of HFT in applications/proposals and reports. These requirements are designed to enable NIH to assess whether extramural research applicants and recipients are adequately assuring compliance with all applicable laws and HHS/NIH policies concerning the acquisition and use of HFT obtained from elective abortion.

NIH requires applicants to address HFT requirements by providing a justification of the use of HFT, details regarding procurement and costs, and information about how the applicant will use HFT. These additional requirements must be met within existing applicable page limits.

Applications and proposals involving HFT that fall within a fundable scoring range will be assessed for policy compliance by an ethics advisory board comprised of scientists, bio-ethicists and others as specified in section 492A of the Public Health Service Act. This committee will assess compliance with HFT policy requirements, including the scientific justification for the use and quantity of HFT proposed, as well as the consideration of alternative models. The committee will review and verify the core ethical principles and procedures used in the process for obtaining written voluntary informed consent for the donation of the tissue and recommend whether, in light of the ethical considerations, NIH should fund the research project.

The addition of research involving HFT from elective abortions to a funded NIH grant project is considered an indicator of a change in scope and, due to the additional information required, such changes will require the submission of a competing revision application. Competing revision applications must include all required information, as described below. For R&D contracts, a modification request to include research involving HFT must undergo technical evaluation and must include all information regarding use and procurement of the tissues. Administrative supplements to add HFT research will not be allowed. Complex grant mechanisms that include centers/cores with discretionary funds will not be allowed to expand existing HFT funding or to add HFT funded activities, including pilot projects.

Training awards and individual fellowships may not propose research using HFT. In addition, grant mechanisms that include centers with discretionary funds and Other Transaction Authority may not be used to support HFT research.