NOT-OD-19-128 (Notice) announces the upcoming HHS requirements and review considerations for NIH research applications (e.g. grants, cooperative agreements, and R&D contracts) that involve the proposed use of human fetal tissue obtained from elective abortions (herein referred to as HFT).
After a recent review of a contract between Advanced Bioscience Resources, Inc. and the Food and Drug Administration, to provide human fetal tissue to develop testing protocols, the Department of Health and Human Services (HHS) was not sufficiently assured that the contract included the appropriate protections applicable to fetal tissue research or met all other procurement requirements. As a result, the contract was terminated (September 2018) and HHS is now conducting an audit of all acquisitions involving human fetal tissue to ensure conformity with procurement and human fetal tissue research laws and regulations. Additionally, HHS initiated a comprehensive review of all research involving fetal tissue to ensure consistency with statutes and regulations, and the adequacy of procedures and oversight of this research.
- Changes apply to competing grant applications submitted for due dates on or after September 25, 2019 and in response to R&D contract solicitations published on or after September 25, 2019
- The Notice does not address changes to the RPPR for currently active awards or the annual progress reports for ongoing contract awards with respect to research including HFT
- Adding research involving HFT to an existing NIH-funded grant would indicate a change in scope and require prior approval through the submission of a competing revision application
- 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 add HFT funded activities, including pilot projects
- Training awards and individual fellowships may not propose research using HFT (see Notice for activity codes). In addition, grant mechanisms that include centers with discretionary funds and Other Transaction Authority may not be used to support HFT research
For the purpose of the requirements of this Notice, research involving HFT 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
This definition of research involving HFT does not include the following:
- Human fetal primary or secondary cell cultures, if cells were not derived from and elective abortion
- Already-established (as of June 5, 2019) human fetal cell lines (e.g. induced pluripontent stem cell lines from human fetal tissue, immortalized cell lines, differentiated cell lines)
- Derivative products from human fetal tissue or cells (e.g. DNA, RNA, protein) if not derived from elective abortion
- Human extra-embryonic cells and tissue, including, but not limited to, umbilical cord tissue, cord blood, placenta, amniotic fluid, and chorionic villi if not derived from elective abortion
- Human fetal cells present in maternal blood or other maternal sources
- Embryonic stem cells or embryonic cell lines
- Research on transplantation of HFT for therapeutic purposes (because of the statutory provision(s) addressing such research)
NOTE: Specific changes to the competing application General Application Guide, Sections G.200, G.300, G.320, and G.400 are implemented in NOT-OD-19-128, and clarified in NOT-OD-19-137 please refer to the Notices when preparing competing applications proposing research involving HFT. The involvement and use of HFT are called-out in the Cover Letter (Section G.200), Detailed Budget and Justification (Section G.300), and Research Plan (Section G.400). Page limits will not be increased to accommodate these requirements. The Modular Budget Form cannot be used (Section G.320). For R&D contract proposals, please refer to the specific solicitation for proposal instructions.
If an NIH research application/proposal proposes the use of HFT as defined above, applicants must address all of the required information in the research plan and the detailed budget as instructed below to avoid being administratively withdrawn and not reviewed:
1. Application and Contract Proposal Research Plan Changes (see clarifying Notice NOT-OD-19-137 for specific changes to the general application guide (R&D contract proposals, please refer to the specific solicitation for proposal instructions)
Section G.220 - R&R Other Porject Information Form
Applicants must include two attachments in the Other Attachments section of the R&R Other Project Information form (Note: if missing these attachments, the application will be administratively withdrawn and not reviewed).
1. HFT Sample IRB Consent Form - blank sample of the IRB approved consent form in a PDF-formatted file named: HFTSampleIRBConsentForm.pdf. The informed consent used for HFT from elective abortion requires language that acknowledges:
- informed consent for donation of HFT was obtained by someone other than the person who obtained informed consent for the abortion,
- occurred afther the informed consent for abortion
- will not affect the method of abortion; no enticements, benefits, or financial incentives were used at any level of the process to incentivize abortion or the donation of HFT
- to be signed by both the woman and the person who obtains the informed consent
2. HFT Compliance Assurance - Letter, signed by the PD/PI, assuring the HFT donating organization or clinic adheres to the requirements of the informed consent process and documentation that HFT was not obtained or acquired for valuable consideration, in a PDF-formatted file named: HFTComplianceAssurance.pdf.
Section G.400 - PHS 398 Resesarch Plan Form
In the Approach section of the Research Strategy, using the heading “Human Fetal Tissue Research Approach” applicants/contract offerors must provide the following details:
- Describe the proposed characteristics, procurement, and procedures for the research use of HFT - description should be sufficiently detailed to permit meaningful evaluation by NIH and an ethics advisory board comprised of scientists, bio-ethicists, and others as specified in section 492A of the Public Health Service Act.
- Justify the use of HFT in the proposed research by indicating
- Why the research goals cannot be accomplished using an alternative to HFT
- What methods were used to determine that no alternatives to HFT can be used (e.g. literature review and preliminary data)
- Results from a literature review used to provide justifications
- Plans for treatment of HFT and the disposal of HFT when research is complete
- Description of planned written, voluntary, informed consent process for cell/tissue donation, or description and documentation of process if cells/tissue were already obtained.
2.Application/Proposal Budget Changes (see Notice for specific changes to Sections G.300 and G.320 of the general application guide. Also reflects clarification of changes to G.300 provided in NOT-OD-199-137. (For R&D contract proposals, please refer to the specific solicitation for proposal instructions)
- Modular budgets will not be accepted, regardless, if HFT costs are proposed or HFT is donated at no cost
- The R&R Budget Form is required and HFT must appear as a separate budget line item (i.e. Section F.8-10 “Other”) whether it is the cost of acquisition or donated. If donated the line item cost will be entered as "0" in the Funds Requested column. DO NOT include costs in Materials and Supplies.
- The line item MUST be titled Human Fetal Tissue Costs and cannot include or be combined with any other costs.
- The budget justification must document the quantity, type(s), and source(s) of the HFT, stage of fetal development, as well as a certification that valuable consideration has not been provided for the acquisition of HFT
- Complex applications that involve an overall budget and multiple project/core budgets, HFT should be included only in each project/core budget where research involving HFT is conducted (even if there is no HFT cost) – ensure that each project/core lists HFT as a separate line item in Section F.8-10 "Other" titled Human Fetal Tissue Costs. Do not include these costs in Materials and Supplies
- For R&D contract proposals, the offeror must sufficiently describe and document in the budget justification section of the proposal, the quantity, type, and source of the HFT. The offer must provide a line item budget cost for acquisition of HFT or indicate the cost is $0.00 if using donated or existing HFT
NIH reminds the research community that the acquisition of HFT is subject to the prohibition in section 498B of the Public Health Service Act, 42 U.S.C. § 289g-2, that it is unlawful to knowingly acquire, receive, or otherwise transfer any HFT for “valuable consideration,” as that term is defined in that section; if the applicant is not proposing to use existing HFT, the applicant is expected to document how he/she will assure that the acquisition of such tissue complies with these legal requirements.
Applications involving HFT will be evaluated using the review criteria presented in the Funding Opportunity Announcement as a significant aspect of the experimental design.
- For grants, evaluation of the scientific appropriateness/justification of the use of HFT will be allowed to affect individual criterion scores for the Approach criterion, and therefore assessments of overall merit and overall impact scores during initial peer review. Comments about the appropriateness/justification of HFT will be included under the Approach review criterion.
- For R&D contracts, this evaluation may affect scores for technical approach, and cost, as examples, and overall technical score during the technical evaluation of proposals. Comments about the appropriateness/justification of HFT will be included under Technical Approach for R&D contracts.
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 the policy requirements in the Notice, including additional consideration of the scientific justification for the use and quantity of HFT, as well as the consideration of alternative models
- 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 ethical considerations) NIH should fund the research project
Grant and cooperative agreement awards with HFT or that add HFT made on or after September 25, 2019 may include the following additional terms and conditions, as needed and on a case by case basis.
The recipient institution including AOR and PD/PI(s) assures that:
- The PD/PI is complying with all applicable laws and HHS/NIH policies specific to HFT.
- Funding for research involving HFT, or continued use of HFT, as defined above, will require justification for the ongoing scientific necessity for the use of HFT in the annual RPPR.
- Informed consents for use of HFT in research, containing certain statements/representations that acknowledges informed consent for donation of HFT was obtained by someone other than the person who obtained the informed consent for abortion, occurred after the informed consent for abortion, and will not affect the method of abortion; no enticements, benefits, or financial incentives were used at any level of the process to incentivize abortion or the donation of HFT; and the informed consent will be signed by both the woman and the person who obtains the informed consent.
- NIH award recipient has documentation from the HFT donating organization assuring adherence to the requirements of the informed consent process and documentation that HFT was not obtained or acquired for valuable consideration. The NIH awardee will acquire this assurance for each year of the award HFT research is conducted for the life of the award and maintain this documentation in accordance with the NIH Record Retention and Access policy (NIH GPS 8.4.2),
- HFT was not obtained or acquired for valuable consideration, as such term is defined in 42 USC § 289g-2.
- The treatment of HFT, and the disposal of HFT when research is complete, should be consistent with the plans outlined in the HFT application justification.