- Explanation of Material Transmitted: NIH Human Research Protection Program (HRPP) policies have been revised to comport with the revised HHS Common Rule (45 CFR 46) and to reflect the newly consolidated IRB structure within the NIH Intramural Research Program. This policy describes the NIH institutional reviews (referred to as “ancillary reviews”) that are required for human subjects research activities, in addition to Institutional Review Board (IRB) review. Upon implementation, this policy partially supersedes SOP 8 Procedures and Required Documentation for Submission.
- Filing Instructions:
- Insert: NIH Manual Chapter 3014-106, dated 08/03/2020
- Implementation Date: 10/12/2020
- PLEASE NOTE: For information on:
- The current policies can also be found at: https://irbo.nih.gov/confluence/display/ohsrp/Policy.
- Content of this chapter, contact the issuing office listed above.
- NIH Policy Manual, contact the Division of Compliance Management, OMA, on (301) 496-4606, or enter this URL: https://oma.od.nih.gov/DMS/Pages/Manual-Chapters.aspx
- Describe the NIH institutional ancillary reviews required for human subjects research activities, in addition to Institutional Review Board (IRB) review.
- This policy applies to NIH investigators conducting human subjects research within the NIH Intramural Research Program (IRP), regardless of whether the NIH IRB or a non-NIH IRB is the Reviewing IRB. For information about ancillary review requirements for institutions relying upon the NIH IRB, see Policy 3014-105 IRB Reliance and Collaborative Research. For information about ethics review and policy, see Policy 3014-102 Investigator Conflict of Interest and Government Royalties.
- In addition to the requirement for IRB review for non-exempt human subjects research conducted by NIH investigators, ancillary reviews may also be required. Ancillary reviews include but are not limited to: Ethics Review, Office of Technology Transfer Review, Scientific Review, Radiation Safety Committee (RSC), Radioactive Drug Research Committee (RDRC), Institutional Biosafety Committee (IBC), and the Select Agent Program (SAP).
- All non-exempt human subjects research conducted by NIH investigators must undergo scientific review consistent with the Policy for Scientific Review of Clinical Protocols Utilizing the NIH Intramural Program, unless waived by the Institute/Center (IC) leadership. All waivers of Scientific Review must be approved by the Chief Scientific Officer, Clinical Center (CC).
- When an NIH IRB is the Reviewing IRB, documentation of approval by the required NIH ancillary review entities must be provided to the NIH IRB.
- When the NIH relies upon a non-NIH Reviewing IRB, approvals by NIH ancillary review entities are still required, and documentation of such approval must be provided to the Office of IRB Operations (IRBO) prior to submission to the Reviewing IRB.
OHSRP has developed a comprehensive glossary of definitions that describe the terms listed below. The glossary can be found at the following link: NIH IRP HRPP Policy Glossary
Note: There may be more than one definition per term, so please review terms carefully to make sure they match the terms listed below. Qualified terms are indicated with a parenthetical qualification. When reviewing a definition, be sure that you are reviewing the appropriate definition that links to this policy. To further assist the reader, each term in the glossary cites the relevant policy number(s) indicating where the term is utilized.
Definitions demarcated with (Pre-2018 Common Rule definition) apply to research approved by an IRB (or deemed to be exempt, or for which no IRB review was required under the regulations) prior to the effective date of the 2018 Common Rule (January 21, 2019).
Definitions demarcated with (2018 Common Rule definition) apply to all research approved by an IRB (or deemed to be exempt, or for which no IRB review was required under the regulations) on or after January 21, 2019, and to research transitioned to the 2018 requirements in accordance with HRPP policy.
- Clinical protocol
- Cooperative Research and Development Agreements (CRADAs)
- Cooperative Research and Development Agreement (CRADA) Review Subcommittee
- Covered Research Protocol
- Non-covered research protocols
- Deputy Ethics Counselors (DECs)
- Dual Use Research of Concern (DURC)
- Human Subject (Pre-2018 Common Rule)
- Human Subject (2018 Common Rule)
- Institutional Biosafety Committee (IBC)
- NIH Investigator
- Office of Technology Transfer (Tech Transfer or OTT)
- Principal Investigator (PI)
- The Radioactive Drug Research Committee (RDRC)
- Radioactive Drug
- The Radiation Safety Committee (RSC)
- Scientific Review (SR)
- Select Agents
- Select Agent Program (SAP)
E. Responsibilities and Requirements
- General Requirements:
- NIH Principal Investigators (PIs) are required to ensure that necessary ancillary reviews are completed and approved prior to initiation of non-exempt human subjects research.
- The IRB Office (IRBO), during its pre-review of a submission, may inform a Principal Investigator that any missing ancillary approval is necessary before the NIH IRB will review or approve the research, or before the protocol can be submitted to a non-NIH IRB for review.
- The Reviewing IRB is responsible for incorporating into the informed consent any language required to be disclosed to a research subject by an ancillary review committee (e.g., disclosure that an investigator on the protocol is listed on the government-owned patent or employee invention report).
- Scientific review:
- The scientific review process applies to clinical protocols (as defined in D. above) and generally occurs at the time of initial protocol review, annual and quadrennial review of the ongoing protocol, and review of substantive modifications to a protocol that pose new scientific questions or substantially alter the scientific approach.
- Intramural Research Program (IRP) PIs are responsible for ensuring clinical protocols involving non-exempt human subjects research have undergone review of scientific content, or obtained a waiver, consistent with the Policy for Scientific Review of Clinical Protocols Utilizing the NIH Intramural Program. This requirement must be met prior to initiating IRB review.
- The Office of IRB Operations (IRBO) will monitor the protocol file to ensure submission of documentation of scientific review (or waiver, if applicable) prior to initiating IRB review of the protocol, consistent with Policy 3014-203 Support of IRB Operations.
- Deputy Ethics Counselor (DEC) Review:
- NIH PIs are responsible for ensuring DEC review of covered research protocols occurs prior to IRB review, as described in Policy 3014-102 Investigator Conflict of Interest and Government Royalties.
- The Radiation Safety Committee (RSC):
- The RSC is responsible for reviewing and approving certain clinical research studies involving exposure of human subjects to ionizing radiation, as described in the RSC charter and policy.
- When there is research radiation use in the protocol that is subject to RSC review, the Principal Investigator must apply to the Radiation Safety Committee for review, consistent with RSC policy. (See information about submissions to the RSC: https://drs.ors.od.nih.gov/rsc/Pages/forms_index.aspx.) If the investigator is unsure whether Radiation Safety Committee review is required s/he should consult with either the RSC or the IRB for guidance.
- The Radioactive Drug Research Committee (RDRC):
- The RDRC is responsible for reviewing and approving the use of certain “non-approved” radioactive drugs for research purposes in humans that would otherwise require review by the FDA in the form of an Investigational New Drug (IND). Use of radioactive drugs in such studies is generally intended to obtain basic research information and is “not intended for immediate therapeutic, diagnostic or similar purposes or to determine the safety and effectiveness of the drug in humans for such purposes (i.e., to carry out a clinical trial)”. (21 CFR 361.1(d)(7)).
- Principal Investigators must follow instructions for submission for RDRC review that can be found at https://drs.ors.od.nih.gov/rsc/RDRC/Pages/rdrc_index.aspx.
- Approval of proposed research may be granted when the RDRC has determined, that the research is in accordance with the standards set forth in 21 CFR 361.1. (See References and https://drs.ors.od.nih.gov/rsc/RDRC/Pages/rdrc_duties.aspx)
- NIH Office of Technology Transfer (Tech Transfer or OTT):
- In cooperation with the technology-transfer offices of the Institutes and Centers (ICs) of the NIH, OTT is responsible for managing the docketing process for securing patents, enforcing terms in the licenses negotiated by the ICs, and managing the royalties collected under those licenses to encourage the development of new products and services to benefit public health.
- Principal Investigators should contact their IC Technology Transfer Office, Technology Development Coordinator, and Licensing & Patenting Managers for assistance in the various phases of the intramural technology transfer processes: review of Employee Invention Reports (EIRs); managing patent prosecution for inventions; licensing available technologies; establishing various agreements, such as Confidential Disclosure Agreements (CDAs), Cooperative Research and Development Agreements (CRADAs), Material Transfer Agreements (MTAs); and Clinical Trial Agreements (CTAs).
- HHS OTT polices can be accessed at HHS Technology Transfer Policies.
- CRADA Subcommittee:
- When a company seeks the right to license inventions made by NIH staff during a clinical trial, the IC Technology Development Coordinator will work with the company and the CRADA Principal Investigator to arrange a CRADA. When the CRADA is ready for execution, the IC Technology Development Coordinator will refer the CRADA to the CRADA Subcommittee for advisory review, and then route the final agreement for signatures.
- When a clinical trial involves a CRADA, the CRADA PI is responsible for notifying the IRB. Specifically, the CRADA PI must inform the IRB when the CRADA partner will receive identifiable human data or identifiable materials.
- The IRB is responsible for ensuring that the appropriate language is included in the informed consent, including disclosure that if applicable, identifiable human data or identifiable materials will be shared with the CRADA partner.
- Institutional Biosafety Committee (IBC):
- The IBC oversees a review and registration process and addresses concerns regarding the Dual Use Research of Concern (DURC) nature of proposed research. The Committee provides recommendations for safety policy to the Director of the NIH or his designee and the DDIR and reviews all infectious disease research performed at BSL-2 and above and any research that falls under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).
- All Principal Investigators (PIs) working with human, plant, or animal pathogens must register their work with the Institutional Biosafety Committee (IBC). This is done through the DOHS electronic biological registration interface (‘PI Dashboard’), which can be accessed through the DOHS Principal Investigators resource page. PIs may consult with IBC contacts, Institute assigned safety specialists, or a Biological Safety Officer, BSO through DOHS at 301-496-2960 if they will be conducting basic and/or clinical research involving recombinant DNA, including human gene transfer, or potentially infectious/toxic materials to ensure that proper containment and biosafety practices are employed.
- All applicable protocols must be submitted in the relevant electronic review system and be reviewed by the NIH IBC.
- Single patient INDs for treatment use of new investigational products that involve use of recombinant DNA, including human gene transfer, or potentially infectious/toxic materials, must be submitted for review if the investigational product has not previously been reviewed or registered by the NIH IBC.
- This decision will be documented in the IBC approved registration which should be submitted with the initial IRB application.
- Principal Investigators considering whether their research constitutes DURC should refer to the NIH Dual-Use Research webpage for information and requirements. All IBC registrations include a series of questions that evaluate the work for DURC. (See References.)
- The NIH Select Agent Program (SAP):
- The SAP manages the oversight of the possession, use, or transfer of selects agents at the NIH. This oversight is performed by the entity assigned Responsible Official (RO) for the SAP. The NIH must comply with the regulations and requirements of 42 CFR 73, 7 CFR 331 and 9 CFR 121.
- Principal Investigators planning to work with select agents/toxins must enroll in the SAP and receive approval prior to the possession, use and transfer of select agents/toxins. It is critical that enrollment in the NIH Select Agent Program occur well in advance of IRB submission. For additional information, training and requirements, see the NIH Select Agent Program webpage. (See References.)
FDA: 21 CFR 361.1
Regarding Select Agents: 42 CFR Part 73, 7 CFR Part 331 and 9 CFR Part 121
Radioactive drugs for certain research uses: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1
- NIH Policy
Policy 3014-102 Investigator Conflict of Interest and Government Royalties.
Policy 3014-105 IRB Reliance and Collaborative Research
Policy 3014-203 Support of IRB Operations
Policies and Procedures to Guide Boards of Scientific Counselors In Reviewing Intramural Research at the NIH https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/review_science/policy-guide_bsc_reviewing_intramural_research.pdf
Policy for Scientific Review of Clinical Protocols Utilizing the NIH Intramural Program: https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/review_science/policy-scientific_review_clinical_protocols.pdf
FDA RDRC Regulations Excerpted from FDA RDRC Regulations (21 CFR 361.1), revised April 1, 2011: https://drs.ors.od.nih.gov/rsc/RDRC/Pages/rdrc_reqpro.aspx
NIH Guidelines for Review of Gene Therapy Trials: https://osp.od.nih.gov/biotechnology/nih-guidelines/
RSC Clinical Protocol and Assistance at https://drs.ors.od.nih.gov/rsc/CPI/Pages/protocol_index.aspx
RSC Forms and Policy Documents webpage at https://drs.ors.od.nih.gov/rsc/Pages/forms_index.aspx.
Work with hazardous biological materials is conducted in compliance with the CDC/NIH publication: Biosafety in Microbiological and Biomedical Laboratories, 5th Edition. https://www.cdc.gov/labs/pdf/CDC-BiosafetyMicrobiologicalBiomedicalLaboratories-2009-P.PDF
Office of Scientific Policy: NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines): https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf
ORS, Division of Occupational Health and Safety: The Role of the PI https://www.ors.od.nih.gov/sr/dohs/YourRole/Pages/PrincipalInvestigators.aspx
ORS, Division of Occupational Health and Safety: NIH IBC Registration Process https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/Registrations.aspx
ORS, Division of Occupational Health and Safety: Select Agent Program https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/select_agents.aspx
ORS, Division of Occupational Health and Safety: Example RD/HPRD Dual Use-Screening Survey. The questions shown are completed in the online biological registration process. https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/RDHPRDSurvey.aspx
NIH, Office of Intramural Research oversight on Dual Use Research: https://oir.nih.gov/sourcebook/ethical-conduct/special-research-considerations/dual-use-research